OncoTargets and Therapy (Jan 2022)

Prognostic Implications of Six Altered Genes in Asian Non-Surgical Esophageal Carcinoma Patients Treated with Chemoradiotherapy

  • Feng A,
  • Yang N,
  • Yu R,
  • Liu J,
  • Pang J,
  • Wu X,
  • Shao Y,
  • Yang Z,
  • Dai H

Journal volume & issue
Vol. Volume 15
pp. 41 – 51

Abstract

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Alei Feng,1,2 Ning Yang,1 Ruoying Yu,3 Jingwen Liu,3 Jiaohui Pang,3 Xue Wu,3 Yang Shao,3,4 Zhe Yang,1 Honghai Dai1 1Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 2Shandong Qidu Pharmaceutical Co. Ltd., Shandong Provincial Key Laboratory of Neuroprotective Drugs, Zibo, 255400, People’s Republic of China; 3Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, People’s Republic of China; 4School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Honghai Dai; Zhe YangTumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaEmail [email protected]; [email protected]: Esophageal cancer (EC), especially esophageal squamous cell carcinoma, remained as one of the most aggressive tumors in China with a five-year survival rate of around 40%. Molecular characteristics through next-generation sequencing are becoming an emerging method in identifying prognostic biomarkers for better treatment management for EC patients.Methods: Targeted next-generation sequencing using a 422-gene pan-cancer panel was performed with tumor tissue samples from a total of 69 Asian non-surgical esophageal carcinoma patients (AEC) treated with chemoradiotherapy. A TCGA cohort of 143 EC patients and another Asian ESCC cohort of 47 patients were employed for validation.Results: In the AEC cohort, alterations in TP53 (94.2%) and NOTCH1 (55.1%) were the two most frequently observed alterations, whereas in the TCGA cohort, only TP53 alterations were observed at a high ratio (85.3%). Co-amplifications of FGF19 and CCND1 were found at a similar ratio in both cohorts. Multiple alterations in the DNA damage pathway were identified but not associated with overall survival in AEC. Using univariate and multivariate Cox regression analyses, six gene alterations including YAP1 amplification, RB1 alteration, BAP1 mutation, MYC amplification, WRN mutation, and BRIP1 mutation were identified as adverse prognostic factors in the AEC cohort. A Cox proportional hazard model based on the six prognosis-related genes was constructed and showed the ability in distinguishing EC patients with poorer disease outcomes in AEC and two validation cohorts.Conclusion: Six gene alterations were found to be potential unfavorable prognostic markers that might provide guidance in the treatment management for EC patients.Keywords: esophageal cancer, YAP1, RB1, BAP1, MYC, BRIP1, WRN, overall survival, chemoradiotherapy

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