Open AccessYAP1 amplification as a prognostic factor of definitive chemoradiotherapy in nonsurgical esophageal squamous cell carcinoma
Author(s) -
Dai Honghai,
Shao Yang W.,
Tong Xiaoling,
Wu Xue,
Pang Jiaohui,
Feng Alei,
Yang Zhe
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2761
Subject(s) - medicine , oncology , cdkn2a , hazard ratio , esophageal squamous cell carcinoma , progression free survival , univariate analysis , cancer , gastroenterology , multivariate analysis , overall survival , confidence interval
Background Definitive chemoradiation therapy (dCRT) is the standard treatment for patients with nonsurgical esophageal squamous cell carcinoma (ESCC), yet patients have demonstrated great variations in their responses to dCRT and inevitably progressed following treatment. Methods To identify prognostic biomarkers, we performed targeted next‐generation sequencing of 416 cancer‐related genes on primary tumors from 47 nonsurgical ESCC patients prior to dCRT treatment. The association between genetic alterations and patients' local recurrence‐free survival (LRFS), progression‐free survival (PFS), and overall survival (OS) was analyzed. Results TP53 (78% of patients), NOTCH1 (32%), ARID1A (13%), FAT1 (13%), and CDKN2A (13%) were commonly mutated in ESCC patients, while gene amplifications frequently occurred in MCL1 (36%), FGF19 (34%), MYC (32%), CCND1 (27%), ZNF217 (15%), CDKN2A (13%), and YAP1 (11%). Univariate and multivariate analyses of clinical factors and genetic alterations indicated that sex is an independent prognostic factor, with males tending to have better LRFS (hazard ratio [HR], 0.25; 95%CI, 0.08‐0.77, P = .015) and progression‐free survival (PFS) (HR, 0.35; 95%CI, 0.13‐0.93, P = .030) following dCRT. Meanwhile, YAP1 amplification (n = 7) was an adverse prognostic factor, and patients with this alteration demonstrated a tendency toward worse outcomes with shorter LRFS (HR, 4.06; 95%CI, 1.26‐13.14, P = .019) and OS (HR, 2.78; 95%CI, 0.95‐8.17, P = .062). In a subgroup analysis, while sex and M‐stage were controlled, a much stronger negative effect of YAP1 amplification vs wild‐type in LRFS was observed (log‐rank P = .0067). Conclusion The results suggested that YAP1 amplification is a potentially useful biomarker for predicting treatment outcomes and identifying patients with a high risk of relapse who should be closely monitored.