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Prognostic analysis and expression patterns of programmed cell death ligand 1 and BRAF V600E in esophageal neuroendocrine carcinoma

  • Authors:
    • Chengcheng Zhang
    • Li Zheng
    • Binwen Xu
    • Guidong Shi
    • Maoyong Fu
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China, Department of Neurosurgery, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan 621000, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 49
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    Published online on: November 25, 2025
       https://doi.org/10.3892/ol.2025.15402
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Abstract

Esophageal neuroendocrine carcinoma (ENEC) is a rare and highly aggressive malignancy. The present study investigated the expression of BRAF V600E and programmed death ligand 1 (PD‑L1) and analyzed prognostic factors affecting patient outcomes. A total of 56 patients diagnosed with ENEC at the Affiliated Hospital of North Sichuan Medical College between January 2019, and September 2024 were retrospectively analyzed. Among them, 39 patients received surgery and were tested for BRAF V600E and PD‑L1 expression using immunohistochemistry. Survival outcomes were estimated using the Kaplan‑Meier method, and prognostic factors were assessed using Cox regression models. BRAF V600E mutations were identified in 12.8% (5/39) of cases, and PD‑L1 expression was positive in 15.4% (6/39). In the mixed neuroendocrine carcinoma and squamous cell carcinoma (MiNEC‑SCC), the positivity rates for both BRAF V600E and PD‑L1 were 33.3% (3/9). Across the entire cohort, the 1‑year overall survival (OS) and progression‑free survival (PFS) rates were 79.7 and 43.1%, respectively, while the 3‑year OS and PFS rates were 49.5 and 25.1%, respectively. Clinical lymph node stage and surgery were notably associated with both OS and PFS. Patients with tumor thickness >1 cm and length >3 cm had markedly worse PFS. Multivariate analysis identified surgery as an independent predictor of improved PFS (P=0.015). Among patients who underwent surgery, postoperative adjuvant therapy was independently associated with improved PFS (P=0.026). In conclusion, BRAF V600E and PD‑L1 were more frequently expressed in the MiNEC‑SCC compared with small cell neuroendocrine carcinoma. Surgery and postoperative adjuvant therapy were notably associated with improved PFS.
View Figures

Figure 1

Flowchart of the present study.

Figure 2

OS and PFS of the entire cohort. (A)
OS of the entire cohort. (B) PFS of the entire cohort. (C) OS of
clinical N0 and N+ groups. (D) PFS of clinical N0 and N+ groups.
(E) OS of surgery and non-surgery groups. (F) PFS of surgery and
non-surgery groups. (G) OS of more aggressive and less aggressive
groups. (H) PFS of more aggressive and less aggressive groups. PFS,
progression-free survival; OS, overall survival; N, node; HR,
hazard ratio; CI, confidence interval.

Figure 3

OS and PFS of the surgical cohort.
(A) OS of the surgical cohort. (B) PFS of the surgical cohort. (C)
OS of patients with adjuvant therapy and without adjuvant therapy
groups. (D) PFS of patients with adjuvant therapy and without
adjuvant therapy groups. PFS, progression-free survival; OS,
overall survival; HR, hazard ratio; CI, confidence interval.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang C, Zheng L, Xu B, Shi G and Fu M: Prognostic analysis and expression patterns of programmed cell death ligand 1 and BRAF V600E in esophageal neuroendocrine carcinoma. Oncol Lett 31: 49, 2026.
APA
Zhang, C., Zheng, L., Xu, B., Shi, G., & Fu, M. (2026). Prognostic analysis and expression patterns of programmed cell death ligand 1 and BRAF V600E in esophageal neuroendocrine carcinoma. Oncology Letters, 31, 49. https://doi.org/10.3892/ol.2025.15402
MLA
Zhang, C., Zheng, L., Xu, B., Shi, G., Fu, M."Prognostic analysis and expression patterns of programmed cell death ligand 1 and BRAF V600E in esophageal neuroendocrine carcinoma". Oncology Letters 31.2 (2026): 49.
Chicago
Zhang, C., Zheng, L., Xu, B., Shi, G., Fu, M."Prognostic analysis and expression patterns of programmed cell death ligand 1 and BRAF V600E in esophageal neuroendocrine carcinoma". Oncology Letters 31, no. 2 (2026): 49. https://doi.org/10.3892/ol.2025.15402
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang C, Zheng L, Xu B, Shi G and Fu M: Prognostic analysis and expression patterns of programmed cell death ligand 1 and BRAF V600E in esophageal neuroendocrine carcinoma. Oncol Lett 31: 49, 2026.
APA
Zhang, C., Zheng, L., Xu, B., Shi, G., & Fu, M. (2026). Prognostic analysis and expression patterns of programmed cell death ligand 1 and BRAF V600E in esophageal neuroendocrine carcinoma. Oncology Letters, 31, 49. https://doi.org/10.3892/ol.2025.15402
MLA
Zhang, C., Zheng, L., Xu, B., Shi, G., Fu, M."Prognostic analysis and expression patterns of programmed cell death ligand 1 and BRAF V600E in esophageal neuroendocrine carcinoma". Oncology Letters 31.2 (2026): 49.
Chicago
Zhang, C., Zheng, L., Xu, B., Shi, G., Fu, M."Prognostic analysis and expression patterns of programmed cell death ligand 1 and BRAF V600E in esophageal neuroendocrine carcinoma". Oncology Letters 31, no. 2 (2026): 49. https://doi.org/10.3892/ol.2025.15402
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