Genomic alterations with impact on survival in esophageal squamous cell carcinoma identified by array comparative...

Risk assessment of esophageal squamous cell carcinoma (ESCC) is currently based on clinicopathological parameters. To identify genomic markers that can predict overall survival in ESCC, we performed array comparative genomic hybridization (array CGH) on a screening set of 35 tumor samples from ESCC patients. Prognosis association of the genes selected on the basis of the array CGH results was further validated by real-time PCR in two independent sample sets (n = 151 and 84). Genomic analysis revealed seven high-level amplifications and two homozygous deletions. Gain of 11q13.2 and loss of 7q34 and 18q21.1-q23 were associated with poor outcome. Gain of 11q13.2 was an independent prognostic factor and was selected for further validation. In both validation sets of samples, copy number increase of CPT1A in 11q13.2 was correlated with short overall survival (P = 0.015, n = 151 and P = 0.044, n = 84). Multivariate analysis confirmed that CPT1A gain provided prognostic information in ESCC (HR, 1.643; 95% CI: 1.076-2.509; P = 0.022; HR, 2.488; 95% CI: 1.235-5.013; P = 0.011). Immunohistochemistry showed significant correlation between strong expression of CPT1A protein and poor outcome of ESCC patients (P = 0.018, n = 73). Our data suggest that gain of CPT1A may be a candidate prognostic factor.