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Esophageal squamous cell carcinoma with EP300 mutations displays distinct genetic characteristics relevant to neoadjuvant chemoradiotherapy

World Journal of Surgical Oncology volume 23, Article number: 1 (2025) Cite this article

Abstract

Background

EP300 mutation is common in esophageal squamous cell carcinoma (ESCC). We aimed to analyze the influence of EP300 mutation on treatment effect and prognosis in ESCC patients underwent neoadjuvant chemoradiotherapy.

Method

Thirty ESCC patients treated with neoadjuvant chemoradiotherapy (nCRT) were enrolled in this study. After assessment of treatment response, transcriptome analyses and immunochemistry were performed for cases in well response or poor response group.

Results

Four of thirty patients harbor EP300 mutation and have poor response to nCRT. Of the remaining 26 nonmutated patients, fifteen patients have a well response, and seven patients have a poor response to nCRT. The EP300-mutated poor response cases have significantly higher immune score than EP300 wild-type poor response cases (P = 0.002), but have no difference from EP300 wild-type well response cases (P = 0.360). Up-regulated B cell related pathways and more CD20 + B cells are in EP300-mutated poor response group, when compared with EP300 wild-type poor response group (P < 0.050). Whereas up-regulated negative regulation of cell death related pathway and higher bcl2 expression level was observed in EP300 mutated poor response group than these in EP300 wild-type well response group (P < 0.050). In prognosis, cases in EP300-mutated poor response group have worse disease-free survival (P = 0.019) and overall survival (P = 0.004) than EP300 wild-type well response group.

Conclusion

EP300 mutated cases have high immune activity in tumor microenvironment. The high anti-apoptosis activity of tumor cells may contribute to resistance to nCRT in EP300-mutated cases.

Background

Esophageal carcinoma is a relatively uncommon cancer with poor prognosis with the five-year survival rate ranges from 15–25% [1, 2] and is affected by biological features and treatment interventions. Esophageal carcinoma accounts for only 1.0% of all estimated new cancer cases, but it has a large estimated deaths, which makes up 2.7% of all estimated deaths in the United States [3]. In China, it also has a high percentage of all estimated new cancer cases (11.1%) as well as all estimated deaths (13.3%) [4]. Squamous cell carcinoma and adenocarcinoma are two main morphological features of esophageal carcinoma. Although squamous cell carcinoma has dropped dramatically during the past years and accounts for less than 50% of esophageal carcinomas in the United States [5, 6], squamous cell carcinoma still accounts for approximately 90% of esophageal carcinomas in China [7]. Over 75% esophageal carcinoma patients are males, and the incidence also increases steadily with age [5, 7, 8].

As esophageal carcinoma is often asymptomatic at an early stage, many patients already have advanced disease at an initial visit. Surgical excision is the main treatment process for esophageal carcinoma patients. With the consideration of poor prognosis, other systematic and local treatments are also applied to reduce relapse and metastasis. The reported data showed that the prognosis was improved after chemotherapy or chemoradiotherapy [9, 10].

Neoadjuvant chemoradiotherapy (nCRT) utilizes chemotherapy and radiotherapy before surgery, offering a way to directly assess therapy response in esophageal carcinoma patients. Clinical trials have demonstrated that nCRT improves prognosis compared to surgery alone in esophageal carcinoma patients [9, 11]. As a standard treatment option for resectable esophageal carcinoma, nCRT still has limited effects on some patients. It is meaningful to shed light on the mechanism of tumor regression under nCRT in different esophageal carcinomas. Some features are reported to be related to the response to nCRT. Infiltrating lymphocytes are common in solid tumors and are reported to be associated with treatment response [12, 13].

EP300 is a commonly mutated gene in esophageal squamous cell carcinoma with a mutation rate of approximately 10% [14, 15]. It belongs to the histone acetyltransferase families and is reported to be a tumor suppressor gene in human cancers [16]. EP300 mutation is reported to be related with poorer prognosis in esophageal squamous cell carcinoma [17]. In bladder cancers, EP300 mutation is reported to promote immune activation [18]. However, the influence of this frequently mutated gene on the immune microenvironment and therapy response in esophageal carcinoma is still unknown.

In this study, we prospectively enrolled esophageal squamous cell carcinoma patients with neoadjuvant chemoradiotherapy. After utilizing whole-exome sequencing, we combined the defined EP300 gene mutation status with the nCRT response to analyze the influence of EP300 mutation on the nCRT response and immune microenvironment.

Method and materials

Patients

The research was approved by the Institutional Review Board of West China Hospital. All patients enrolled in this study signed an informed consent form. From January 2018 to October 2019, these patients were diagnosed with localized esophageal squamous cell carcinoma. Prior to initiating neoadjuvant chemoradiotherapy, venous blood and tumor samples were collected form all patients through endoscopic ultrasound examination. The inclusion and exclusion criteria are detailed in Fig. 1.

Fig. 1
figure 1

Flowchart of this study

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Neoadjuvant treatment protocol

Delivery of radiotherapy was performed by radiation oncologists, with a total dose of 41.4–50.4 Gy (23–28 fractions). The gross tumor volume (GTV) was defined as all the visible primary tumors and involved regional lymph nodes. The clinical target volume (CTV) included the GTV with a 3-centimeter (cm) expansion in the cranial-caudal direction, metastatic lymph node with a 0.5-1.0-cm expansion in the cranial-caudal direction and 0.5-cm radially. A further 0.5-cm circumferential expansion from the CTV was used to generate the planning target volume (PTV). All patients were treated using intensity-modulated radiotherapy (IMRT) technique. Meanwhile, systemic chemotherapy was given concurrently with radiotherapy, with a chemotherapy scheme of platinum and paclitaxel: paclitaxel 135–150 mg/m2 day 1 + cisplatin 25 mg/m2 day 1–3 or carboplatin (AUC 5) day 1, repeated every 21–28 days. The adverse events for each patient were recorded and assessed following the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

Surgical procedure

All the patients underwent Meakown esophagectomy with cervical anastomosis, including lymphadenectomy, replacement of the esophagus with the stomach, and esophagogastrostomy with layered and esophageal-gastric anastomosis. All of those patients received 3-field lymph node dissection and the mean numbers and stations of harvested lymph nodes were 23.6 ± 7.2 and 13.2 (9–23), respectively.

Histopathologic response assessment

Before neoadjuvant chemoradiotherapy, tumor samples were obtained through endoscopic biopsy. The histology subtype was confirmed by at least two pathologists. Following neoadjuvant chemoradiotherapy, tumor samples from surgical excision were collected for further analysis. The differences in microscopic characteristics between the pre-treatment samples and post-treatment samples were compared and assessed according to criteria from the CAP (College of American Pathologists)/NCCN (The National Comprehensive Cancer Network). The lymph nodes were also assessed by these criteria. For both primary tumor and lymph nodes combined, the tumor regression score (TRS) has four levels: TRS 0 (pathology complete response (pCR), no tumor cell in primary site and lymph node), TRS 1 (nearly pCR, single or small cluster tumor cells in primary site and lymph node), TRS 2 (partly pCR, residual tumor cells with stromal fibrosis, and TRS 3 (no reaction, no or minor loss of tumor cells).

EP300 somatic mutation analyses

Whole-exome sequencing (WES) technology was employed to analyze the differences in somatic mutations between the two groups. The pretreatment tumor samples from patients were collected with white blood cells obtained prior to treatment serving as a comparison. Following DNA extraction and quality assessment, library construction and exon capture were performed, after which raw data were generated using the Illumina platform af. The raw data were filtered, mapped, and annotated for further analysis. The EP300 mutation data were extracted from these sequencing data and divided cases into EP300 mutated and wild-type groups. All EP300-mutated cases had pathological remission of TRS 2/3. To clarify the difference in treatment response between EP300 mutated and wild-type cases, we only selected TRS 0 to be present as the well response group, and TRS2/3 as the poor response group for further study.

Transcriptome analyses

Pretreatment tumor samples from patients were used, and the differences in gene expression and related biological processes of patients between the well response group (TRS 0) and poor response group (TRS 2/3) were analyzed by RNA sequencing. The extracted RNA was subjected to quality inspection, library construction, and sequencing based on the Illumina sequencing platform to obtain raw data.

Immunochemistry (IHC) analyses

Hematoxylin-eosin (H&E) and IHC staining were performed on 4 μm formalin-fixed-paraffin-embedded (FFPE) tissues from enrolled patients. CD4 (SP35, MXB Biotechnologies, China), CD8 (SP16, MXB Biotechnologies, China), CD20 (L26, MXB Biotechnologies, China), CD21 (EP64, MXB Biotechnologies, China), Ki67 (MXR002, MXB Biotechnologies, China), bcl-2 (MX022, MXB Biotechnologies, China)), and p300 (D8Z4E, Cell Signaling Technology, USA) were used to perform IHC staining on each sample according to the manufacturer’s instructions. The percentage of membrane staining of CD4, CD8, CD20, and CD21 on tumor-infiltrating lymphocytes was recorded for further analyses. The percentage of nuclear staining of Ki67 and p300 and membrane/cytoplasm staining of bcl2 on tumor cells were also recorded.

Statistical analyses

Tumor purity was evaluated based on stromal score and immune score, which were calculated by the estimate package on transcriptome data. The immune cell subsets infiltrating on each sample were estimated by EPIC, a deconvolution algorithm based on transcriptome data. A total of 1,794 distinct immune-related genes were obtained from the Immunology Database for further immunology studies. Principal component analysis (PCA) of immune-related genes was performed to show the two-dimensional distribution of enrolled cases. After adjusting for tumor purity, genes with an absolute value of fold change (FC) > 1.5 and P value < 0.001 were regarded as significantly differentially expressed genes between the two groups by the DeSeq2 package. Gene set enrichment analysis (GSEA) was used to assess gene set differences between two groups by the clusterProfiler package. To show the immune cell subset distribution, we conducted single-set GSEA (ssGSEA) on each sample by the GSVA package. All packages were operated in RStudio software version 1.4.1103 (RStudio, Inc., Boston, MA, USA). The prognosis of enrolled patients was evaluated through disease-free survival (DFS) and overall survival (OS). DFS was defined as the interval time from surgery to the detection of disease relapse or any cause of death. OS was defined as the interval time from surgery to death. The survival analyses were performed using the Kaplan-Meier method. The survival curves were compared using the log-rank test. All survival analyses were conducted using SPSS software version 25.025 (IBM Corporation, Armonk, NY, USA). A two-tailed P value < 0.050 was considered statistically significant.

Results

Overview of EP300 mutation status

The top 30 genes exhibiting the highest mutation frequencies are presented based on the mutation evaluation rate of each gene, as shown in Supplementary Fig. 1. TP53 is identified as the most frequently mutated gene, with a mutation frequency reaching up to 90% (27/30). The subsequent genes include TTN (46.7%, 14/30), PIK3CA (26.7%, 8/30), MUC5B (23.3%, 7/30), CDKN2A (23.3%, 7/30), NOTCH (20%, 6/30), HTT (20%, 6/30), NBPF10 (16.7%, 5/30), MUC2 (16.7%, 5/30), FSIP2 (16.7%, 5/30), FAT1 (16.7%, 5/30), among others, as illustrated in Supplementary Fig. 1.

Pretreatment specimens from thirty patients were tested for EP300 mutation status by Next Generation Sequencing (NGS). Four patients harbor EP300 mutations (Fig. 2A), of which three patients have missense mutations in the HAT domain (p.Y1414C, p.D1507V, and p.E1514K) and one patient has stop-gain mutation (p.S195G). After nCRT, all these four patients have TRS 2/3. Of the remaining of 26 nonmutated patients, fifteen patients have TRS 0, and seven patients have TRS 2/3. In this study, we finally enrolled 26 patients who had TRS0 (well response group) or TRS2/3 (poor response group) into further study and divided these patients into three subgroups: EP300-mutated poor response, EP300-wild-type poor response, and EP300-wild-type well response. In the final enrolled cases, the EP300 expression level is not influenced by mutation status in the transcriptome (P = 0.878, Fig. 3C) or IHC data (P = 0.758, Fig. 3D). The characteristics of the enrolled cases are listed in Table 1 and supplementary Table 1. The baseline characteristics are not different among the three groups (P > 0.05, Table 1).

Table 1 Pretreatment features of cases in the EP300-mutated poor response, EP300 wild-type poor response, and EP300 wild-type well response groups
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Case relationships among the three groups

A summary of variant classifications for the 26 samples was presented in supplementary Fig. 2. Higher TMB was found in EP300 mutated poor response, compared to either EP300 wild-type poor response cases (P<0.05) or EP300-wild-type well response group (P<0.01). (supplementary Fig. 2H)

Based on transcriptome data, we estimated tumor purity for each enrolled case. The stromal score, immune score, and tumor purity in each group are shown in Fig. 2E-G. EP300 mutated poor response cases have significantly higher immune score than EP300 wild-type poor response cases (P = 0.002, Fig. 2F), but have no difference from EP300 wild-type well response cases (P = 0.360, Fig. 2F). On tumor purity assessment, the tumor purity in EP300 mutated cases was lower than that in cases of poor response (P = 0.014, Fig. 2G).

To further test the immune-related differences among the three subgroups, we used 1794 immune-related genes to perform cluster analyses. In PCA (Fig. 2H), all four EP300 mutated poor response cases and 10 (66.7%) EP300 wild-type well response cases are classified into the PC1 positive dimension. Only one (14.3%) EP300 wild-type poor response cases are in the PC1 positive dimension. To confirm the relationship of enrolled cases among the three groups, we then conducted Pearson correlation of each sample based on immune-related gene expression (Fig. 2I). There are two main clusters in the Pearson correlation. The four EP300-mutated poor response cases and 10 (66.7%) EP300-wild-type well response cases are in the same cluster. However, only 2 (28.6%) EP300 wild-type poor response cases are in the above cluster.

Fig. 2
figure 2

Overview of EP300-mutated and wild-type esophageal squamous cell carcinomas. (A) Four mutation sites detected in this study. (B) Immunohistochemistry (IHC) staining of p300. (a) and (c) are examples of HE and IHC staining of p300-negative cases, respectively. (b) and (d) are examples of HE and IHC staining of p300-positive cases, respectively. (C) Normalized expression of EP300 in EP300-mutated and wild-type cases from transcriptome data. (D) Positive rate in EP300-mutated and wild-type cases from IHC analyses. The stromal score (E), immune score (F), and tumor purity (G) were calculated using transcriptome data and compared between the EP300-mutated poor response, EP300 wild-type poor response, and EP300 wild-type well response groups. (H) PCA of enrolled cases by immune-related genes. (I) Pearson correlation of enrolled cases by immune-related genes. (*P < 0.05, **P < 0.01)

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Differentially expressed immune-related genes among the three groups

After adjusting for the tumor purity of each case, the differentially expressed genes were compared between the three subgroups. Clustering analyses showed distinctions about immune-related genes between the EP300-mutated and wild-type poor response groups, as well as EP300 wild-type well response and poor response groups (Fig. 3A and C). However, the differentially expressed immune-related genes did not separate the EP300-mutated poor response group and the wild-type well response group (Fig. 3E).

Then, we analyzed the differences in pathways between groups. Immune-related pathways, especially B-cell-related pathways, are significantly upregulated in the EP300-mutated poor response and EP300 wild-type well response groups compared with EP300 wild-type poor response group (P < 0.001, Fig. 3B and D). However, immune-related pathways do not show a significant difference between the EP300-mutated poor response group and the wild-type well response group. The negative regulation of cell death-related pathways was upregulated in the EP300-mutated poor response group compared with the EP300 wild-type well response group (P = 0.029, Fig. 3F).

Fig. 3
figure 3

Differentially expressed immune-related genes and gene ontology (GO) analyses between the three groups. (A) Cluster analyses of differentially expressed immune-related genes between the EP300-mutated and wild-type poor response groups. (B) GO analyses show the differences in immune-related biological process (BP) between EP300-mutated and wild-type poor response groups. (C) Cluster analyses of differentially expressed immune-related genes between the EP300 wild-type well response and poor response groups. (D) GO analyses show the differences in immune-related BP between EP300 wild-type well response and poor response groups. (E) Cluster analyses of differentially expressed immune-related genes between the EP300-mutated poor response and EP300 wild-type well response groups. (F) GO analyses show nonimmune-related BP and molecular function between the EP300-mutated poor response and EP300 wild-type well response groups

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Different distributions of immune cell subsets among the three groups

As immune-related genes and pathways showed differences among the three subgroups, we then checked the distinction of immune cell subsets in each subgroup. The ssGSEA showed similar immune cell distributions between the EP300-mutated poor response group and the EP300 wild-type well response group (Fig. 4A). We further calculated the percentage of immune cell subsets by EPIC based on transcriptome data. The B-cell subset was significantly higher in the EP300-mutated poor response group (P = 0.012) and wild-type well response group (P = 0.032) than in the wild-type poor response group (Fig. 4D). The CD4 + and CD8 + T-cell subsets were not different among the three groups (Fig. 4B and C).

The IHC analyses showed that CD20 + B cells were more abundant in the EP300-mutated poor response group (P = 0.036) and wild-type well response group (P = 0.049) than in the wild-type poor response group (Fig. 4H). However, the CD4 + and CD8 + T cells are not different among the three subgroups (Fig. 4F and G). We then analyzed proliferation and apoptosis markers expressed in tumor cells. Higher bcl2 expression levels were observed in the EP300-mutated poor response group than in the EP300 wild-type well response group (P = 0.007, Fig. 4L).

Fig. 4
figure 4

Immune cell subsets for enrolled cases. (A) Immune cell subsets calculated by ssGSEA using transcriptome data. Cluster analyses show the relationship about immune cell subset scores among cases. Percentage of CD4 + T cells (B), CD8 + T cells (C), and B cells (D) estimated by EPIC on transcriptome data. (E) Examples of positive immunohistochemistry (IHC) staining of CD4 (a), CD8 (b), CD20 (c), and CD21 (d) for infiltrating immune cells in tumor tissues. Percentage of CD4+ (F), CD8+ (G), CD20+ (H), and CD21+ (H) cells in the three groups. J. Examples of positive IHC staining of Ki67 (a) and bcl2 (b) in tumor cells. Percentage of ki67 (K) and bcl2 (L) positive tumor cells in the three groups

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Survival analyses among the three subgroups

During the follow-up time (ranging from 0 to 19 months), 6 patients had recorded disease recurrence, and 6 patients died of this disease. The EP300 wild-type well response group had superior DFS and OS than the EP300-mutated poor response group (P = 0.019 and P = 0.004) and EP300 wild-type poor response group (P = 0.009 and P = 0.001, Fig. 5A and B). However, DFS and OS were not different between the EP300-mutated and wild-type poor response groups (P = 0.761 and P = 0.661, Fig. 5A and B).

Fig. 5
figure 5

Disease-specific survival (A) and overall survival (B) in the three groups

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Discussion

In this study, we investigated the impact of EP300 mutation on the response to nCRT and immune microenvironment in esophageal squamous cell carcinomas. All four EP300-mutated cases were resistant to nCRT, achieving only TRS2 or TRS3 responses. When compared with the EP300 wild-type well response and poor response groups, the immune microenvironment in EP300-mutated cases was found to be similar to that of the EP300 wild-type well response group.

Among 30 consecutively prospectively enrolled patients, four were identified as having EP300 mutations. This mutation rate aligns with findings from other studies, which report approximately 10% prevalence [14, 15]. Three out of these four patients presented missense SNVs in the histone acetyltransferase (HAT) region of EP300 (Fig. 2A). One of four patients has an EP300 stop-gain mutation at prior to the HAT region (Fig. 2A). Analysis of transcriptomic and immunohistochemical data revealed that the EP300 somatic mutation status has no influence on EP300 expression level (Fig. 2C and D). These results suggest that such mutations had no effects on EP300 expression routinely detected by the transcriptome and IHC methods.

However, the structure and function of p300 may be influenced by mutations. A study conducted by Gao et al. [15] reported that EP300 mutation at the HAT region did not alter its expression but could potentially silence its tumor-suppressive functions. Additionally, ome studies indicated that mutated EP300 may promote immune activation in various cancers [18, 19]. In this investigation, we ategorized cases into three groups based on their EP300 mutation status and response to nCRT. EP300-mutated cases had higher immune scores, indicating an activated immune system in these cases (Fig. 2F). When comparing immune-related features among the three groups, we found that EP300-mutated cases had a closer relationship with the EP300 wild-type well response group but distinct differences from the EP300 wild-type poor response group in PCA (Fig. 2H) and Pearson relationship analyses (Fig. 2I). The differential expression analyses also showed upregulated immune-related biological processes (BP) in the EP300-mutated poor response group compared with the EP300 wild-type poor response group (Fig. 3B). These findings indicate that although cases harboring mutations in EP300 exhibit resistance to nCRT, they possess an activated immune system akin to that observed in well-responsive cases with wild-type EP300.

Some studies have demonstrated the significant role of immune cells in response to adjuvant therapy for solid tumors [20]. A high immune cell infiltration rate in the peritumoral region is correlated with a preferable treatment response and prognosis [20]. The higher immune cell infiltration before treatment indicates high host immune activity, which may have a synergistic effect with cytotoxic treatment for successful tumor eradication [21]. However, some cases with a high immune cell infiltration rate did not respond well to nCRT. The individual differences in the treatment response of cases with a high immune cell infiltration rate prompted us to search for the causes. In this study, we found that the EP300 wild-type well response group had upregulated B-cell-mediated immunity compared with the EP300 wild-type poor response group (Fig. 3D). The EPIC and IHC analyses also showed a higher proportion of B cells in the EP300 wild-type well response group than in the EP300 wild-type poor response group (Fig. 4D and H). Some studies have indicated that, although B cells constitute only a small fraction of tumor-infiltrating lymphocytes, they play a crucial role in stabilizing the function of T-cell subpopulations [22, 23]. Furthermore, it has been demonstrated that B cells are associated with improved prognosis in solid tumors [22, 24,25,26].

However, EP300-mutated cases in our study also exhibited upregulated B-cell-mediated immunity compared with the EP300 wild-type poor response group (Fig. 3B). These mutated cases had a similar high proportion of B cells as the EP300 wild-type well response group (Fig. 4D and H). Nevertheless, all these mutated cases are resistant to nCRT and had a poor prognosis than the EP300 wild-type well response group (Fig. 5). The enhanced immune system in EP300-mutated cases does not correlate with a favorable response to nCRT or improved prognosis. These findings indicates that other gene sets may paly roles in resistance to nCRT in EP300-mutated cases.

Then, we utilized the nonimmune-related genes that were differentially expressed between the EP300-mutated poor response and wild-type well response groups to conduct GSEA. The EP300-mutated cases had higher molecular function of transcription regulator activity and BP of negative regulation of cell death (Fig. 3F). Bcl2 promotes tumor cell proliferation by inhibiting programmed cell death or apoptosis [27]. It is correlated with resistance to cytotoxic treatment in multiple tumor types [28]. In our study, IHC data showed that bcl2 was highly expressed in EP300-mutated cases, which was significantly higher than that in the EP300 wild-type well response group (Figs. 4L and 48% vs. 17%, P = 0.007). EP300-mutated cases also had a similar high ki67 positive rate as the EP300 wild-type well response group, but without statistical significance (Figs. 4K and 48% vs. 32%, P = 0.196).

As p300 interacts with CREB-binding protein (CBP) and plays crucial roles in acetylation, EP300 mutations may influence the function of acetyltransferase. Acetylation may occur on both histone and nonhistone proteins. This kind of posttranslational modification has been proven to regulate all cellular processes [29]. In solid tumors, protein acetylation on lysine residues regulates the activities of oncoproteins [30, 31]. Acetylation by p300/CBP could promote tumor progression [32]. We found EP300-mutated cases had poorer prognosis than wild-type cases in esophageal squamous cell carcinomas. However, the impact of mutated EP300 on protein acetylation still needs further study in esophageal squamous cell carcinomas.

There were several limitations in this study. First, the study is limited by the small sample size of the cases, which inevitably limited the generalization of the results and the sequential conclusions. Second, the study lacks functional exploration and mechanism verification in experiments and the conclusion still needs to be verified through functional experiments in our further study. In the limitation part, we have added the related discussions on this issue. In addition, the analysis of HPV, P53, and dendritic cells—factors of paramount importance—will be explored in a subsequent study. It is essential to recruit additional cases of esophageal carcinoma with the EP300 mutation to validate these findings.

In this study, we identified distinct characteristics in esophageal squamous cell carcinomas with EP300 mutations.The comparison analyses with EP300 wild-type well response group and poor response group revealed that EP300 mutated cases have similar high immune activity in tumor microenvironment with EP300 wild-type well response group. However, elevated anti-apoptotic activity observed in tumor cells contributes to resistance to neoadjuvant chemoradiotherapy (nCRT) in EP300-mutated cases. The combination of high immune activity and treatment resistance underscores the uniqueness of EP300-mutated esophageal squamous cell carcinomas. Of note, the small sample size of the study inevitably limited the generalization of the results and the impact of mutated EP300 on protein acetylation still needs further study in esophageal squamous cell carcinomas. Nevertheless, the findings of distinct genetic characteristics relevant to neoadjuvant chemoradiotherapy in EP300-mutated esophageal squamous cell carcinoma provide a new insight in the treatment of ESCC neoadjuvant chemoradiotherapy.

Data availability

Sequence data have been deposited at the Genome Sequence Archive for Human (GSA-Human), which is hosted by the National Genomics Data Center (NGDC) (Accession：HRA007232）

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Acknowledgements

Not applicable.

Funding

The study was supported by the Science Foundation project in Sichuan Province (2021JDKP0046 and 2021YFQ0029).

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Author notes

  1. Yutian Lai and Yingxian Dong were considered as co-first authors.

Authors and Affiliations

  1. Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China

    Yutian Lai, Yingxian Dong, Long Tian & Yang Hu

  2. Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China

    Yutian Lai, Yingxian Dong & Long Tian

  3. West China Hospital of Medicine, Sichuan University, Chengdu, 610041, P.R. China

    Hongjun Li

  4. Department of Endoscopy Center, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China

    Xinyi Ye

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  1. Yutian Lai
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  3. Long Tian
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  4. Hongjun Li
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  6. Yang Hu
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Contributions

YL and YD made the study design, data collection and interpretation, and manuscript writing. LT, HL, and XY participated in the data collection. YH contributed in the study design. YH, YL, and YD did the final approval of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yang Hu.

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Ethics approval and consent to participate

The research was approved by the Institutional Review Board of West China Hospital. All patients enrolled in this study signed an informed consent form.

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The authors declare no competing interests.

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Lai, Y., Dong, Y., Tian, L. et al. Esophageal squamous cell carcinoma with EP300 mutations displays distinct genetic characteristics relevant to neoadjuvant chemoradiotherapy. World J Surg Onc 23, 1 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12957-024-03642-9

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12957-024-03642-9

Keywords

World Journal of Surgical Oncology

ISSN: 1477-7819

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