Background: 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