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Gene mutation, clinical characteristics and pathology in resectable lung adenocarcinoma

World Journal of Surgical Oncology volume 23, Article number: 16 (2025) Cite this article

Abstract

Objective

With the wide use of CT scan in clinical practice, more lung cancer was diagnosed in resectable stage. Pathological examination and genetic testing have become a routine procedure for lung adenocarcinoma following radical resection. This study analyzed special pathological components and gene mutations to explore their relationship with clinical characteristics and overall survival.

Methods

Clinical, pathological, and gene mutation data from 1,118 patients were collected. All patients underwent surgery at the Department of Thoracic Surgery, the Second Xiangya Hospital of Central South University. Patients were grouped based on pathological components and gene mutations. Differences in clinical features and overall survival were analyzed as well.

Results

Patients with mucinous, neuroendocrine, and poor-differentiated components were presented with more prognostic risk factors, including pleural invasion, carcinothrombosis, STAS, and advanced stages, along with varying frequencies of gene mutations. These factors significantly shortened overall survival. ALK and KRAS mutations were also associated with risk factors such as solid nodules, pleural invasion, STAS, and later stages. However, a significant reduction in overall survival was observed only in patients with the KRAS mutation. Relationship between gene mutations and pathological components still requires further investigation.

Conclusion

Special pathological components (mucinous, neuroendocrine, and poor-differentiated) and gene mutations had an influence on biological behavior of tumors, resulting in different clinical characteristics and prognosis.

Introduction

Lung cancer ranks first globally in both incidence and mortality rates [1]. With the increased use of CT scans due to COVID-19 [2], a significant number of early-stage lung cancers have been detected, leading to a higher proportion of patients eligible for surgical resection [3]. Targeted therapy has rapidly advanced in lung cancer treatment, playing a crucial role not only in maintenance therapy but also in neoadjuvant and adjuvant settings [4]. The effective use of targeted therapy relied on next-generation sequencing (NGS). Epidermal growth factor receptor (EGFR) was the first target identified in lung cancer treatment, showing significant survival advantages over chemotherapy [5]. Since then, mutations such as anaplastic lymphoma kinase (ALK) fusion, ROS1 fusion, Kirsten rat sarcoma (KRAS), RET, and mesenchymal to epithelial transition factor (MET) have also been discovered [6]. These driver gene mutations lead to different clinical characteristics and survival outcomes among patients with different mutations.

Pathological examination remained the gold standard for tumor diagnosis, providing comprehensive insight for lung cancer. Lung adenocarcinoma was classified into several pathological subtypes, such as lepidic, acinar, papillary, micropapillary and solid. Previous studies have shown that micropapillary and solid components were correlated with poor prognosis [7,8,9]. Other rare types like mucinous and neuroendocrine components can be observed [10]. Although prior researches have investigated the characteristics of these populations, comprehensive comparisons across multiple cohorts were lacking [11]. Lung cancer was often initially detected via CT scans, with common manifestations including solid or ground-glass opacity (GGO) [12]. Identifying the relationship between imaging features, gene mutations, and pathological components can aid in clinical decision-making for patients.

For resectable lung cancer, clinical characteristics, pathology and gene mutations are almost unavoidable topics. This study aimed to investigate the differences in clinical characteristics and prognosis among various lung adenocarcinoma populations by focusing on pathological components and gene mutations.

Methods

Informed consent and ethics

The institutional review board ethics committee of the the Second Xiangya Hospital of Central South University approved the study protocol and publication of data (ethical approval number: LYF2021096). The individuals provided written informed consent for the publication of the study data. Data security and privacy were protected throughout the study.

Patients

All patients were diagnosed with resectable lung cancer and have undergone radical surgery in the department of thoracic surgery, the Second Xiangya Hospital of Central South University. Patients must be diagnosed with lung adenocarcinoma according to pathological results. And all patients have received next-generation sequencing (NGS). Unsuccessful surgery, non-malignant lesions and other pathological types were excluded. The final pathological cancer stages were assessed according to the eighth edition of the Union for International Cancer Control and American Joint Committee on Cancer TNM classification.

Collection of data

All the clinical and pathological features were collected in the system in the Second Xiangya Hospital of Central South University. In total, 1118 patients were collected between 2017 and 2022 and last follow-up was done in May 2024.

Group by pathology

The whole population was divided into four groups by pathological diagnosis. 1) Mucinous group: lung adenocarcinoma with mucinous component. 2) Neuroendocrine group: lung adenocarcinoma with neuroendocrine component accounting for less than 50%. 3) Poor-differentiated group: lung adenocarcinoma with poor differentiation (solid and micropapillary). 4) Reference group: lung adenocarcinoma without any component mentioned in former three groups.

Histological evaluation and gene mutation analysis

Resected surgical specimens were cut at 3-mm intervals and fixed in 10% buffered formalin. Embedded in paraffin, all specimens were stained with H&E for histological examination. Two pathologists reviewed the specimens and categorized the histological subtype of each tumor according to the classification of lung adenocarcinoma. The expression of PD-L1 was evaluated using combined positive score (CPS) using specimens from surgical resection. Gene mutation was examined using the next generation sequencing methods performed by geneplus.

Statistical analysis

All statistical analyses were performed using R Studio (R 4.3.1 version), difference between clinical features and gene mutations were evaluated using t test and χ2 test. All figures are created using R Studio (R 4.3.1 version) and Adobe Illustrator 2020. All tables are created using Microsoft Word and Excel.

Results

Clinical and pathological features in all patients and among four groups

Clinical and pathological features across the four groups are summarized in Table 1, while comparisons of PD-L1 levels are shown in Supplementary Fig. 1 and 2. The number of smokers was significantly higher in the poor-differentiated group. A higher proportion of solid nodules was observed in the poor-differentiated and mucinous groups. Tumors in the poor-differentiated, mucinous, and neuroendocrine groups were generally more invasive, as evidenced by higher rates of pleural invasion, carcinothrombosis, and STAS. However, only poor-differentiated and mucinous tumors were significantly associated with more advanced cancer stages. In the neuroendocrine group, early-stage tumors were more likely to metastasize distantly, often resulting in unresectable disease. Conversely, the lepidic component, known as a protective factor for lung cancer patients [7], was significantly less prevalent in the poor-differentiated, mucinous, and neuroendocrine groups. Higher PD-L1 levels were observed in male smokers with solid manifestation on CT scans, patients with advanced disease or invasive pathological components.

Table 1 Clinical and pathological features among for groups. p value was calculated compared with reference group using χ2 test (p < 0.05: *, p < 0.01: **, p < 0.001: ***). GGO: ground glass opacity. STAS: spread through air space
Full size table

Gene mutation status in all patients and among four groups

Gene mutation status across the four groups was summarized in Table 2 and Fig. 1. Gene mutation status of our cohort aligned with typical findings in Asian patients [13]. In the mucinous group, there was a significantly lower rate of EGFR mutation, accompanied by a higher incidence of KRAS mutation and ALK fusion. At ELCC 2024, mucinous lung adenocarcinoma was reported to have fewer TP53 and BRAF mutations, but we did not observe this in our study. Similarly, higher mutation frequencies of STK11, SMARCA4, NKX2-1, and GNAS reported in other studies could not be validated in our cohort either (Fig. 1). In the neuroendocrine group, EGFR mutation was also less frequent. Mutations such as ROS1 fusion, MET, and RET could rarely be seen in both the mucinous and neuroendocrine groups. In the poor-differentiated group, only a higher rate of KRAS mutations was noted. Based on the gene mutation profiles, the mucinous and neuroendocrine groups appeared more distinct, whereas tumor cells in the poor-differentiated group showed greater similarity to the reference group.

Table 2 Gene mutation rate for EGFR, ALK, KRAS, ROS1, RET and MET in four groups
Full size table
Fig. 1
figure 1

Other gene mutations related to mucinous group

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Additional characteristics of gene mutation in all patients were summarized in Supplementary Fig. 3 and 4. Among patients with KRAS mutation, EX2 was predominant (88%), while EX3 was less common (12%). The most frequent KRAS mutation subtypes were G12C (38.7%), G12D (20%), and G12V (17.3%). For patients with EGFR mutation, EX19 and EX21 accounted for the majority of subtypes (32.6% and 48.7%, respectively), with EX18 and EX20 representing 5.7% and 9.7%, respectively. Furthermore, correlations between different mutations were analyzed, but no evidence of positive relationships between any two mutations was found. Interestingly, EGFR mutations tended to exclude the coexistence of other gene mutations.

Clinical and pathological features between different gene mutation status

Clinical and pathological features according to mutation status were shown in Table 3 and Supplementary Table 1. Patients with EGFR mutation was more often female and non-smokers, while KRAS mutation was more frequently observed in male patients with smoking history. In patients with EGFR mutation, more nodules were presented with GGO. In contrast, patients with ALK fusion or KRAS mutation exhibited more solid nodules.

Table 3 Pathological features between gene mutation status. p value was calculated compared with reference group using χ2 test (p < 0.05: *, p < 0.01: **, p < 0.001: ***). STAS: spread through air space
Full size table

Increased pleural invasion was observed in ALK fusion + patients and more STAS was shown in both ALK fusion + /KRAS + patients with later stage. EGFR + patients had a higher likelihood of harboring lepidic and micropapillary components, while ALK fusion + patients showed more solid and micropapillary components. In patients with KRAS mutation, fewer lepidic components and more solid components were presented. PD-L1 levels were higher in patients with ALK and KRAS mutations (Supplementary Fig. 2).

Survival analysis

Survival results related to clinicopathological features are summarized in Fig. 2, while the survival outcomes related to genetic mutations could be seen in Fig. 3. Overall survival analysis indicated poorer outcomes for the poor-differentiated, mucinous, and neuroendocrine groups. Among the common driver mutations, only KRAS mutation was associated with a shortened overall survival for patients. This may due to the use of targeted therapy after surgery, which mitigates the aggressive nature associated with the gene mutation. The poor prognosis of mucinous group may also be linked to the high frequency of KRAS mutation. Furthermore, patients presenting with GGO had longer overall survival, confirming that solid components were a risk factor for prognosis. Both STAS and micropapillary components were identified as adverse prognostic factors [7, 14], but no significant differences were observed concerning pleural invasion and carcinothrombosis. Although the survival period was shorter in the poor-differentiated population, the presence of well-differentiated components (lepidic) did not significantly impact prognosis. Lastly, patients exhibiting higher PD-L1 expression were found to have shorter overall survival.

Fig. 2
figure 2

Comparison of overall survival times between clinical and pathological features. A: among four groups, B: N stage, C: stage, D: pleural invasion, E: carcinothrombosis, F: STAS, G: lepidic component, H: solid component, I: micropapillary component, J: CT manifestation, K: PD-L1 level

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Fig. 3
figure 3

Comparison of overall survival times between genetic mutations. A: EGFR mutation, B: ALK fusion, C: KRAS mutation, D: EGFR mutation subtypes, E: KRAS mutation subtypes

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Discussion

Clinical and pathological characteristics in four groups

Lung mucinous adenocarcinoma has been reported with lower lobe predominance, bilateral involvement, distinguishing gene mutation patterns (higher KRAS mutation) and poorer prognosis [15, 16], with consistent results in our study. However, the nodules of lung mucinous adenocarcinoma typically lack imaging features on CT [15], making biopsy crucial for accurate diagnosis [17]. Studies from 2016 to 2023 compared lung mucinous adenocarcinoma with large cohorts of non-mucinous adenocarcinoma [16, 17], but no significant differences in clinical characteristics or survival have been found. Additionally, neither mixed adenocarcinoma components nor postoperative chemotherapy significantly affect overall survival [17]. In terms of gene mutation, there was a high rate of ALK fusion but with poorer prognosis compared with reference group, which may be the result of the invasive nature of mucinous component. Moreover, relationship between KRAS mutation and immunotherapy remained complicated [18,19,20], which will be discussed later.

Among lung adenocarcinomas, neuroendocrine carcinomas (e.g., small cell lung cancer) was known for aggressiveness, early metastasis, and relatively poor prognosis [21]. Around 2000, a number of physicians studied the effectiveness of surgical treatment for such patients, but only a subset of studies concluded that > 5% of neuroendocrine differentiation components can affect survival [22]. In addition, incidence of driver mutation on this group was investigated but without international peer review [11]. However, in our cohort, the relative high proportion of EGFR mutation, possibly representing an intermediate state in the transformation of EGFR-positive lung adenocarcinoma into small cell lung cancer [23]. Moreover, mechanisms and examples of conversion to SCLC from NSCLC with targeted therapies (mainly EGFR) have been studied previously [14, 24, 25]. And we believed that our study will help to gain a more in-depth understanding of this process, which can facilitate personalized medicine, such as modification of chemotherapy regimens, closer detection of distal metastases (especially brain metastases), prophylactic radiotherapy.

In our study, poor-differentiation was defined as the presence of micropapillary or solid component, which has been explored by many researchers [7,8,9] and were generally associated with aggressive biological behavior [7]. The amount of micropapillary component (> = 5%) was a widely accepted predictor of poorer prognosis [8]. Lepidic component was regarded as protective factors of NSCLC, so that sublobular resection was proposed for patients with lepidic differentiation as early as 2017 [9]. Subsequent studies indicated that lepidic component was a positive prognostic factor in GGO [26], tumors < 3 cm [27] and all lung adenocarcinoma patients [28]. However, other research has reported that the presence of lepidic component did not improve survival outcomes [7]. In our cohort, patients with micropapillary component were presented with shorter overall survival, whereas there was no significant difference related to solid or lepidic differentiation. Considering the low percentage of these subgroups, statistical error stemming from insufficient sample size could occur so that prospective studies of larger scale will be needed. Notably, 80% of our patients were T1 (881/1104) and micropapillary component had an impact on survival, whereas solid component did not, partially validating the results of previous studies [14]. These results suggested that relying solely on the maximum diameter of the primary tumor (T-stage) couldn’t fully predict the impact of the poor-differentiated component or guide adjuvant therapy for patients with stage IA NSCLC either [29]. Fortunately, the predictive role of ctDNA-based minimal residue disease (MRD) monitoring has been demonstrated recently in resectable NSCLC patients with a maximum diameter of the primary tumor greater than 2 cm [30]. Longitudinal ctDNA-based MRD detection could predict most of recurrence (87.2%, 41/47) and the survival benefits were not limited to staging, with the limitation of undetectable brain recurrence [31,32,33]. As the risk factors for postoperative adjuvant therapy in stage I lung cancer patients remain inconclusive [29, 34], ctDNA-based MRD monitoring may be an option for patients with poorly differentiated components. However, given that postoperative recurrence in driver gene-positive lung adenocarcinoma (especially EGFR mutations) predominantly involves brain metastases (27.4%, 29/106) [35,36,37], such detection methods need further improvement before being applicable in clinical practice. We believe that with advancements in biomedical science and the continuous investigation of clinical trials, cancer patients will undoubtedly receive more precise diagnoses and treatments in the future.

The impact of gene mutation on clinical/pathological features and prognosis

It was widely accepted that EGFR mutation was more frequent in Asian female patients without smoking history [38], and similar results were shown in our patients. However, whether EGFR was related to GGO remained controversial [7, 39]. Our result showed a higher prevalence of EGFR mutation in GGO and confirmed results by Li et al. [40]. But this result wasn't consistent with review published by Cheng et al. [38], in which no significant difference was observed. Howevever, no survival impacts of EGFR + mutation was shown. Additionally, ALK fusion was possibly associated with lymph node metastasis and pleura invasion [41,42,43], with more solid and micropapillary components potentially leading to poorer prognosis [44, 45]. However, we failed to find significant difference between ALK fusion + / ALK fusion—patients in survival analysis, which may due to low percentage of the subgroup. KRAS mutation could always be seen in male smokers and its influence on prognosis remained unclear [46]. In our cohort, KRAS mutation was related to poor prognosis, which may be the result of more invasive nature without standard targeted therapy. While existing medical treatments have provided limited benefits to this group of patients, the emergence of new therapies offers a silver lining. With the meticulous study of the KRAS mutation and developments of biochemistry [47], nowadays it is possible to directly target KRAS with small molecular inhibitors [48]. Allele-specific KRAS G12C inhibitors such as Sotorasib [49, 50] and Adagrasib [51] have entered phase III clinical trials with ORR of 28.1%-45.9%. Also, articles on Divarasib (KRAS G12C inhibitors) in NSCLC patients have been published with the ORR of 53.4% [52], while new KRAS inhibitors including G12C inhibitors, G12D inhibitors, multi-RAS inhibitors and immune therapies were being investigated in phase-I studies [48, 53, 54]. However, resistance were usually observed in patients using KRAS inhibitors, including primary resistance [55,56,57], adaptive resistance [58,59,60] and histological transformation [61,62,63]. As a consequence, it’s crucial to investigate co-occurring genetic mutations and baseline transcriptional features of KRAS pathway, developing new mutation-selective inhibitors and panRAS/KRAS inhibitors. What’s more, combination therapies will also play an important role in improving prognosis. When treating lung cancer, KRAS inhibitors could be combined with RTK inhibition [59], SOS1 and SHP2 inhibitors [48], downstream MAPK blockade [64, 65] and immunotherapy [57, 66, 67]. With the gradual completion of KRAS inhibitors for lung cancer, it is expected to play an important role in (neo)adjuvant settings and contributing to better prognosis for patients.

Overall, tumors with driver mutations tend to be more aggressive thus more likely to metastasize (especially to the brain [68,69,70,71]), and targeted therapies were able to suppress tumor growth thus improve prognosis. However, the availability of targeted drugs varied greatly depending on hospital resources and the financial capabilities. In China, genetic testing for cancer has not been included in the national health insurance system and is primarily conducted by third-party companies, imposing a significant financial burden on patients. Additionally, negative test results, or positive results that fail to result in promising efficacy of targeted therapy, deter some patients from undergoing genetic testing. As such, more robust evidence linking gene mutation and prognosis needed to be obtained in phase III randomized controlled trials (RCT)s, narrowing the scope of genetic testing to improve detection rates while reducing the burden on patients.

The level of PD-L1 between different patients

PD-L1 testing has already become a routine immunohistochemical assay and was also used as a biomarker predicting the efficacy of immunotherapy [72]. According to previous analyses, only patients with BRAF and MET mutations tended to benefit from immunotherapy, while high PD-L1 expression in ALK/ROS1/RET fusions and KRAS mutations did not translate into survival benefits of immunotherapy [73, 74]. In addition, patients with EGFR mutations benefited very little from immunotherapy especially in exon19/21 subtype or with T790M [73, 75], with some even developing hyperprogression [76, 77]. As a consequence, most patients with gene mutation (especially EGFR mutation, ALK and ROS1 fusions) were largely excluded from studies of immunotherapy until the emergence of combination therapy in 2021 [73]. Nowadays, treatments on EGFR-TKIs resistant patients were being progressively investigated (ORIENT-31, KEYNOTE-789, TATTON, IMpower150, ATLANTIC and CheckMate 722), but the benefit was still limited. Efficacy will be improved with the addition of antiangiogenic therapy [78,79,80], but may lead to intolerable adverse effects or even lead to drug discontinuation. It is now widely believed that the poor efficacy of immunotherapy in driver mutation-positive patients is related to the tumor microenvironment (TME). It is confirmed that CD8 + T cell infiltration was reduce in EGFR + patients with the increasing of tumor mutation burden (TMB), making the tumor “cold” [73]. In addition, tumor-associated macrophages [81], CD4 + T cells [82] and other stromal cells [83] were involved to prevent cytotoxic immune cells from infiltrating and result in poor efficacy. On the other hand, resistance could be overcome if TME was modified by some treatments [84,85,86]. In our cohort, high PD-L1 levels were related to gene mutation and poorer prognosis, consistent with previous studies [87,88,89,90,91]. Overall, our study provided a piece of evidence for the relationship between gene mutation and PD-L1 levels in resecatble lung adenocarcinoma. Moving forward, research should focus on benefiting patients with gene mutation and high PD-L1 expression by immunotherapy.

Limitations

This was a single-center retrospective cohort study, which was prone to geographical and institutional biases that might affect generalizability. Geographically, our patients mainly came from Hunan Province so the results could only represent the clinicopathological or genetic feature of a single region. Institutionally, single-center studies may be influenced by clinical practices and data quality of our department. Other limitation included lost of follow-up, small sample size and low proportion of certain subgroups (e.g., ALK fusion +). In this article, we compared the results of previous studies and treatment guidelines to mitigate the impact of these limitations. However, stronger conclusions required more rigorous study designs and larger sample sizes.

Conclusion

In our patients, tumors with mucinous, neuroendocrine, and poor-differentiated components were presented to be more invasive, with differing gene mutation status and association with poorer prognosis. For these patients, adjuvant and neoadjuvant therapies should be considered based on gene mutation and immunohistochemistry results, and techniques such as MRD can also be used for postoperative monitoring thereby potentially increasing the cure rate. However, patients with driver gene mutation may not benefit from immunotherapy regardless of high PD-L1 expression. As a result, research into the tumor microenvironment, mutation subtypes and new immunotherapeutic markers may make a difference. Overall, this study provided new analytical perspectives for postoperative pathological components and gene mutation, which need to be confirmed by studies of larger scale and may contribute to the development of precision medicine in the future.

Data availability

No datasets were generated or analysed during the current study.

References

  1. Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–49.

    Article  PubMed  Google Scholar 

  2. Yuan Y, et al. The development of COVID-19 treatment. Front Immunol. 2023;14:1125246.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Oudkerk M, et al. Lung cancer LDCT screening and mortality reduction - evidence, pitfalls and future perspectives. Nat Rev Clin Oncol. 2021;18(3):135–51.

    Article  PubMed  Google Scholar 

  4. Tan AC, Tan DSW. Targeted Therapies for Lung Cancer Patients With Oncogenic Driver Molecular Alterations. J Clin Oncol. 2022;40(6):611–25.

    Article  PubMed  CAS  Google Scholar 

  5. Mok TS, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–57.

    Article  PubMed  CAS  Google Scholar 

  6. Herrera-Juárez M, et al. Targeted therapy for lung cancer: Beyond EGFR and ALK. Cancer. 2023;129(12):1803–20.

    Article  PubMed  Google Scholar 

  7. Wang Z, et al. Invasive adenocarcinoma manifesting as pure ground glass nodule with different size: radiological characteristics differ while prognosis remains the same. Transl Cancer Res. 2021;10(6):2755–66.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zhang Y, et al. A comprehensive investigation of molecular features and prognosis of lung adenocarcinoma with micropapillary component. J Thorac Oncol. 2014;9(12):1772–8.

    Article  PubMed  CAS  Google Scholar 

  9. Cox ML, et al. The Role of Extent of Surgical Resection and Lymph Node Assessment for Clinical Stage I Pulmonary Lepidic Adenocarcinoma: An Analysis of 1991 Patients. J Thorac Oncol. 2017;12(4):689–96.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Succony L, et al. Adenocarcinoma spectrum lesions of the lung: Detection, pathology and treatment strategies. Cancer Treat Rev. 2021;99:102237.

    Article  PubMed  CAS  Google Scholar 

  11. Li X, et al. Clinical Characteristics, Treatment and Prognosis of 47 Non-small Cell Lung Cancer with Neuroendocrine Differentiation Patients. Zhongguo Fei Ai Za Zhi. 2019;22(8):507–11.

    PubMed  Google Scholar 

  12. Sun F, et al. Ground glass opacities: Imaging, pathology, and gene mutations. J Thorac Cardiovasc Surg. 2018;156(2):808–13.

    Article  PubMed  CAS  Google Scholar 

  13. Dearden S, et al. Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap). Ann Oncol. 2013;24(9):2371–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Fu F, et al. Distinct Prognostic Factors in Patients with Stage I Non-Small Cell Lung Cancer with Radiologic Part-Solid or Solid Lesions. J Thorac Oncol. 2019;14(12):2133–42.

    Article  PubMed  Google Scholar 

  15. Kim DH, et al. Radiological and clinical features of screening-detected pulmonary invasive mucinous adenocarcinoma. Interact Cardiovasc Thorac Surg. 2022;34(2):229–35.

    Article  PubMed  Google Scholar 

  16. Cui D, Xie S, Liu Q. Postoperative survival of pulmonary invasive mucinous adenocarcinoma versus non-mucinous invasive adenocarcinoma. BMC Pulm Med. 2023;23(1):9.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Luo J, et al. Analysis of the clinicopathologic characteristics and prognostic of stage I invasive mucinous adenocarcinoma. J Cancer Res Clin Oncol. 2016;142(8):1837–45.

    Article  PubMed  Google Scholar 

  18. Passiglia F, et al. Efficacy of nivolumab in pre-treated non-small-cell lung cancer patients harbouring KRAS mutations. Br J Cancer. 2019;120(1):57–62.

    Article  PubMed  CAS  Google Scholar 

  19. Amanam I, et al. Role of immunotherapy and co-mutations on KRAS-mutant non-small cell lung cancer survival. J Thorac Dis. 2020;12(9):5086–95.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Adderley H, Blackhall FH, Lindsay CR. KRAS-mutant non-small cell lung cancer: Converging small molecules and immune checkpoint inhibition. EBioMedicine. 2019;41:711–6.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Wang WZ, et al. Small cell lung cancer: Subtypes and therapeutic implications. Semin Cancer Biol. 2022;86(Pt 2):543–54.

    Article  PubMed  CAS  Google Scholar 

  22. Dai Y, Han B. Research advance on non-small cell lung carcinoma with neuroendocrine differentiation. Zhongguo Fei Ai Za Zhi. 2011;14(2):165–9.

    PubMed  CAS  Google Scholar 

  23. Quintanal-Villalonga A, et al. Multiomic Analysis of Lung Tumors Defines Pathways Activated in Neuroendocrine Transformation. Cancer Discov. 2021;11(12):3028–47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Bai W, et al. Clinicopathological features of patients with transformation from EGFR mutant lung adenocarcinoma to small cell lung cancer. Transl Cancer Res. 2021;10(8):3694–704.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Gardner EE, et al. Lineage-specific intolerance to oncogenic drivers restricts histological transformation. Science. 2024;383(6683):eadj1415.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Mimae T, et al. Role of ground-glass opacity in pure invasive and lepidic component in pure solid lung adenocarcinoma for predicting aggressiveness. JTCVS Open. 2022;11:300–16.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sato D, et al. Lepidic growth component as a favorable prognostic factor in non-small cell lung cancer of ≤3 cm. Thorac Cancer. 2022;13(23):3274–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Huang S, et al. Incorporation of the lepidic component as an additional pathological T descriptor for non-small cell lung cancer: Data from 3335 cases of lung adenocarcinoma. Lung Cancer. 2024;189:107472.

    Article  PubMed  CAS  Google Scholar 

  29. Riely GJ, et al. Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2024;22(4):249–74.

    Article  PubMed  CAS  Google Scholar 

  30. Zhang JT, et al. Longitudinal Undetectable Molecular Residual Disease Defines Potentially Cured Population in Localized Non-Small Cell Lung Cancer. Cancer Discov. 2022;12(7):1690–701.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Li YS, et al. Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy. Ann Oncol. 2018;29(4):945–52.

    Article  PubMed  CAS  Google Scholar 

  32. Yang H, et al. Cerebrospinal fluid-derived circulating tumor DNA is more comprehensive than plasma in NSCLC patients with leptomeningeal metastases regardless of extracranial evolution. Heliyon. 2022;8(12):e12374.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Seoane J, et al. Cerebrospinal fluid cell-free tumour DNA as a liquid biopsy for primary brain tumours and central nervous system metastases. Ann Oncol. 2019;30(2):211–8.

    Article  PubMed  CAS  Google Scholar 

  34. Abbosh C, et al. Implementing circulating tumor DNA as a prognostic biomarker in resectable non-small cell lung cancer. Trends Cancer. 2024;10(7):643–54.

    Article  PubMed  CAS  Google Scholar 

  35. Passaro A, et al. Adjuvant Treatments for Surgically Resected Non-Small Cell Lung Cancer Harboring EGFR Mutations: A Review. JAMA Oncol. 2023;9(8):1124–31.

    Article  PubMed  Google Scholar 

  36. Xu ST, et al. The Unique Spatial-Temporal Treatment Failure Patterns of Adjuvant Gefitinib Therapy: A Post Hoc Analysis of the ADJUVANT Trial (CTONG 1104). J Thorac Oncol. 2019;14(3):503–12.

    Article  PubMed  CAS  Google Scholar 

  37. Herbst RS, et al. Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non-Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial. J Clin Oncol. 2023;41(10):1830–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Cheng Z, et al. CT characteristics of non-small cell lung cancer with epidermal growth factor receptor mutation: a systematic review and meta-analysis. BMC Med Imaging. 2017;17(1):5.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Li D, et al. Ten-Year Follow-up Results of Pure Ground-Glass Opacity-Featured Lung Adenocarcinomas After Surgery. Ann Thorac Surg. 2023;116(2):230–7.

    Article  PubMed  Google Scholar 

  40. Huo JW, et al. Radiological classification, gene-mutation status, and surgical prognosis of synchronous multiple primary lung cancer. Eur Radiol. 2022;32(6):4264–74.

    Article  PubMed  CAS  Google Scholar 

  41. Li P, et al. Comparison of Clinicopathological Features and Prognosis between ALK Rearrangements and EGFR Mutations in Surgically Resected Early-stage Lung Adenocarcinoma. J Cancer. 2019;10(1):61–71.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kim TH, et al. CT Characteristics of Non-Small Cell Lung Cancer With Anaplastic Lymphoma Kinase Rearrangement: A Systematic Review and Meta-Analysis. AJR Am J Roentgenol. 2019;213(5):1059–72.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Shin SH, et al. Anaplastic lymphoma kinase rearrangement in surgically resected stage IA lung adenocarcinoma. J Thorac Dis. 2018;10(6):3460–7.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Travis WD, et al. Introduction to The 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart. J Thorac Oncol. 2015;10(9):1240–2.

    Article  PubMed  Google Scholar 

  45. Yang H, et al. Relationship between EGFR, ALK Gene Mutation and Imaging and Pathological Features in Invasive Lung Adenocarcinoma. Zhongguo Fei Ai Za Zhi. 2022;25(3):147–55.

    PubMed  Google Scholar 

  46. Reck M, et al. Targeting KRAS in non-small-cell lung cancer: recent progress and new approaches. Ann Oncol. 2021;32(9):1101–10.

    Article  PubMed  CAS  Google Scholar 

  47. Cox AD, Der CJ. KRAS takes the road to destruction. Science. 2024;385(6715):1274–5.

    Article  PubMed  CAS  Google Scholar 

  48. Singhal A, Li BT, O’Reilly EM. Targeting KRAS in cancer. Nat Med. 2024;30(4):969–83.

    Article  PubMed  CAS  Google Scholar 

  49. de Langen AJ, et al. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS(G12C) mutation: a randomised, open-label, phase 3 trial. Lancet. 2023;401(10378):733–46.

    Article  PubMed  Google Scholar 

  50. Skoulidis F, et al. Sotorasib for Lung Cancers with KRAS p.G12C Mutation. N Engl J Med. 2021;384(25):2371–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Jänne PA, et al. Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRAS(G12C) Mutation. N Engl J Med. 2022;387(2):120–31.

    Article  PubMed  Google Scholar 

  52. Sacher A, et al. Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation. N Engl J Med. 2023;389(8):710–21.

    Article  PubMed  CAS  Google Scholar 

  53. Popow J, et al. Targeting cancer with small-molecule pan-KRAS degraders. Science. 2024;385(6715):1338–47.

    Article  PubMed  CAS  Google Scholar 

  54. Kim D, et al. Pan-KRAS inhibitor disables oncogenic signalling and tumour growth. Nature. 2023;619(7968):160–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Dy GK, et al. Long-Term Outcomes and Molecular Correlates of Sotorasib Efficacy in Patients With Pretreated KRAS G12C-Mutated Non-Small-Cell Lung Cancer: 2-Year Analysis of CodeBreaK 100. J Clin Oncol. 2023;41(18):3311–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Negrao MV, et al. Comutations and KRASG12C Inhibitor Efficacy in Advanced NSCLC. Cancer Discov. 2023;13(7):1556–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Thummalapalli R, et al. Clinical and Genomic Features of Response and Toxicity to Sotorasib in a Real-World Cohort of Patients With Advanced KRAS G12C-Mutant Non-Small Cell Lung Cancer. JCO Precis Oncol. 2023;7:e2300030.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Hallin J, et al. Anti-tumor efficacy of a potent and selective non-covalent KRAS(G12D) inhibitor. Nat Med. 2022;28(10):2171–82.

    Article  PubMed  CAS  Google Scholar 

  59. Gulay KCM, et al. Dual Inhibition of KRASG12D and Pan-ERBB Is Synergistic in Pancreatic Ductal Adenocarcinoma. Cancer Res. 2023;83(18):3001–12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Ryan MB, et al. KRAS(G12C)-independent feedback activation of wild-type RAS constrains KRAS(G12C) inhibitor efficacy. Cell Rep. 2022;39(12):110993.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Li Z, et al. Alveolar Differentiation Drives Resistance to KRAS Inhibition in Lung Adenocarcinoma. Cancer Discov. 2024;14(2):308–25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Tong X, et al. Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer. Cancer Cell. 2024;42(3):413-428.e7.

    Article  PubMed  CAS  Google Scholar 

  63. Schoenfeld AJ, et al. Tumor Analyses Reveal Squamous Transformation and Off-Target Alterations As Early Resistance Mechanisms to First-line Osimertinib in EGFR-Mutant Lung Cancer. Clin Cancer Res. 2020;26(11):2654–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Yaeger R, et al. Molecular Characterization of Acquired Resistance to KRASG12C-EGFR Inhibition in Colorectal Cancer. Cancer Discov. 2023;13(1):41–55.

    Article  PubMed  CAS  Google Scholar 

  65. Misale S, et al. KRAS G12C NSCLC Models Are Sensitive to Direct Targeting of KRAS in Combination with PI3K Inhibition. Clin Cancer Res. 2019;25(2):796–807.

    Article  PubMed  CAS  Google Scholar 

  66. Chour A, et al. Brief Report: Severe Sotorasib-Related Hepatotoxicity and Non-Liver Adverse Events Associated With Sequential Anti-Programmed Cell Death (Ligand)1 and Sotorasib Therapy in KRAS(G12C)-Mutant Lung Cancer. J Thorac Oncol. 2023;18(10):1408–15.

    Article  PubMed  CAS  Google Scholar 

  67. Schoenfeld AJ, et al. Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinib. Ann Oncol. 2019;30(5):839–44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Ge M, et al. High probability and frequency of EGFR mutations in non-small cell lung cancer with brain metastases. J Neurooncol. 2017;135(2):413–8.

    Article  PubMed  CAS  Google Scholar 

  69. Iuchi T, et al. Frequency of brain metastases in non-small-cell lung cancer, and their association with epidermal growth factor receptor mutations. Int J Clin Oncol. 2015;20(4):674–9.

    Article  PubMed  CAS  Google Scholar 

  70. Li WY, et al. The role of EGFR mutation as a prognostic factor in survival after diagnosis of brain metastasis in non-small cell lung cancer: a systematic review and meta-analysis. BMC Cancer. 2019;19(1):145.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Shin DY, et al. EGFR mutation and brain metastasis in pulmonary adenocarcinomas. J Thorac Oncol. 2014;9(2):195–9.

    Article  PubMed  CAS  Google Scholar 

  72. Yu H, et al. PD-L1 Expression in Lung Cancer. J Thorac Oncol. 2016;11(7):964–75.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Dantoing E, et al. Anti-PD1/PD-L1 Immunotherapy for Non-Small Cell Lung Cancer with Actionable Oncogenic Driver Mutations. Int J Mol Sci. 2021;22(12):6288.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Brody R, et al. PD-L1 expression in advanced NSCLC: Insights into risk stratification and treatment selection from a systematic literature review. Lung Cancer. 2017;112:200–15.

    Article  PubMed  Google Scholar 

  75. Negrao MV, et al. Oncogene-specific differences in tumor mutational burden, PD-L1 expression, and outcomes from immunotherapy in non-small cell lung cancer. J Immunother Cancer. 2021;9(8):e002891.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Kato S, et al. Hyperprogressors after Immunotherapy: Analysis of Genomic Alterations Associated with Accelerated Growth Rate. Clin Cancer Res. 2017;23(15):4242–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Ferrara R, et al. Hyperprogressive Disease in Patients With Advanced Non-Small Cell Lung Cancer Treated With PD-1/PD-L1 Inhibitors or With Single-Agent Chemotherapy. JAMA Oncol. 2018;4(11):1543–52.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Lu S, et al. Sintilimab plus chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer with disease progression after EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): second interim analysis from a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Respir Med. 2023;11(7):624–36.

    Article  PubMed  CAS  Google Scholar 

  79. Lu S, et al. Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2022;23(9):1167–79.

    Article  PubMed  CAS  Google Scholar 

  80. Park S, et al. Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non-Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04). J Clin Oncol. 2024;42(11):1241–51.

    Article  PubMed  CAS  Google Scholar 

  81. Wang L, et al. PD-L1-expressing tumor-associated macrophages are immunostimulatory and associate with good clinical outcome in human breast cancer. Cell Rep Med. 2024;5(2):101420.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Chen Y, et al. Implications of PD-L1 expression on the immune microenvironment in HER2-positive gastric cancer. Mol Cancer. 2024;23(1):169.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Hu L, et al. Expression, regulation, and function of PD-L1 on non-tumor cells in the tumor microenvironment. Drug Discov Today. 2024;29(11):104181.

    Article  PubMed  CAS  Google Scholar 

  84. Liu YT, Sun ZJ. Turning cold tumors into hot tumors by improving T-cell infiltration. Theranostics. 2021;11(11):5365–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Chen Q, Sun T, Jiang C. Recent Advancements in Nanomedicine for “Cold” Tumor Immunotherapy. Nanomicro Lett. 2021;13(1):92.

    PubMed  PubMed Central  CAS  Google Scholar 

  86. Giustarini G, Pavesi A, Adriani G. Nanoparticle-Based Therapies for Turning Cold Tumors Hot: How to Treat an Immunosuppressive Tumor Microenvironment. Front Bioeng Biotechnol. 2021;9:689245.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Azuma K, et al. Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. Ann Oncol. 2014;25(10):1935–40.

    Article  PubMed  CAS  Google Scholar 

  88. Li C, et al. PD-L1 expression with respect to driver mutations in non-small cell lung cancer in an Asian population: a large study of 1370 cases in China. Ther Adv Med Oncol. 2020;12:1758835920965840.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Karatrasoglou EA, et al. Association between PD-L1 expression and driver gene mutations in non-small cell lung cancer patients: correlation with clinical data. Virchows Arch. 2020;477(2):207–17.

    Article  PubMed  CAS  Google Scholar 

  90. Tsuta K, et al. RET-rearranged non-small-cell lung carcinoma: a clinicopathological and molecular analysis. Br J Cancer. 2014;110(6):1571–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Dudnik E, et al. BRAF Mutant Lung Cancer: Programmed Death Ligand 1 Expression, Tumor Mutational Burden, Microsatellite Instability Status, and Response to Immune Check-Point Inhibitors. J Thorac Oncol. 2018;13(8):1128–37.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

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Funding

National Natural Science Foundation of China (grant number 82172879).

Natural Science Foundation of Hunan Province for Distinguished Young Scholars (grant number 2022JJ10096).

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Authors and Affiliations

  1. Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China

    Ji’an Zou, Wei Han, Yan Hu, Chao Zeng, Jina Li, Weixuan Lei, Jieming Cao, Quanming Fei, Mengqi Shao, Junqi Yi, Zeyu Cheng, Li Wang & Wenliang Liu

  2. Hunan Key Laboratory of Early Diagnosis and Precision Treatment of Lung Cancer, The Second Xiangya Hospital of Central South University, Changsha, China

    Ji’an Zou, Wei Han, Yan Hu, Chao Zeng, Jina Li, Weixuan Lei, Jieming Cao, Quanming Fei, Mengqi Shao, Junqi Yi, Zeyu Cheng, Li Wang & Wenliang Liu

  3. Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China

    Fang Wu

  4. Hunan Cancer Mega-Data Intelligent Application and Engineering Research Centre, Changsha, Hunan, 410011, China

    Fang Wu

  5. Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China

    Fang Wu

  6. Hunan Key Laboratory of Early Diagnosis and Precision Therapy in Lung Cancer, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China

    Fang Wu

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  1. Ji’an Zou
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  2. Wei Han
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  12. Li Wang
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  13. Fang Wu
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  14. Wenliang Liu
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Contributions

Ji’an Zou wrote the main manuscript and participated in all figures and tables. Wei Han, Yan Hu, Chao Zeng, Jina Li has taken part in data analysis and revision of the article. Weixuan Lei, Jieming Cao, Quanming Fei, Mengqi Shao, Junqi Yi, Zeyu Cheng were involved in data curation. Li Wang aquired the funding. Fang Wu revised the whole article. Wenliang Liu has supervised the whole process of the research.

Corresponding author

Correspondence to Wenliang Liu.

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Ethics approval and consent to participate

The institutional review board ethics committee of the the Second Xiangya Hospital of Central South University approved the study protocol and publication of data (ethical approval number: LYF2021096). The individuals provided written informed consent for the publication of the study data. Data security and privacy were protected throughout the study.

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The authors declare no competing interests.

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Supplementary Information

12957_2025_3680_MOESM1_ESM.pdf

Supplementary Material 1. Supplementary Figure 1: Difference of PD-L1 between clinical characteristics. A: smoke, B: sex, C: manifestation on CT, D: N stage, E: stage, F: Group.

12957_2025_3680_MOESM2_ESM.pdf

Supplementary Material 2. Supplementary Figure 2: Difference of PD-L1 between gene mutations. A: EGFR mutation, B: ALK fusion, C: KRAS mutation.

12957_2025_3680_MOESM3_ESM.pdf

Supplementary Material 3. Supplementary Figure 3: Mutation subtypes of EGFR and KRAS in all patients. A: subtypes of EGFR mutation, B/C: subtypes of KRAS mutation.

12957_2025_3680_MOESM4_ESM.pdf

Supplementary Material 4. Supplementary Figure 4: Correlations between mutations. There will be ✕ in the grid if p<0.05.

Supplementary Material 5.

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Zou, J., Han, W., Hu, Y. et al. Gene mutation, clinical characteristics and pathology in resectable lung adenocarcinoma. World J Surg Onc 23, 16 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12957-025-03680-x

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Keywords

World Journal of Surgical Oncology

ISSN: 1477-7819

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