Prognostic significance of CDK6 amplification in esophageal squamous cell carcinoma

Abstract

Dysregulation of CDK6 plays crucial roles in the carcinogenesis of many kinds of human malignancies. However, the role of CDK6 in esophageal squamous cell carcinoma (ESCC) is not well known. We investigated the frequency and prognostic value of CDK6 amplification to improve the risk stratification in patients with ESCC. Pan-cancer analysis of CDK6 was conducted on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases. CDK6 amplification was detected in 502 ESCC samples by Fluorescence in situ hybridization (FISH) through tissue microarrays (TMA). Pan-cancer analysis revealed that CDK6 mRNA level was much higher in multiple kinds of cancers and higher CDK6 mRNA level indicated a better prognosis in ESCC. In this study, CDK6 amplification was detected in 27.5% (138/502) of patients with ESCC. CDK6 amplification was significantly correlated with tumor size (p = 0.044). Patients with CDK6 amplification tended to have a longer disease-free survival (DFS) (p = 0.228) and overall survival (OS) (p = 0.200) compared with patients without CDK6 amplification but of no significance. When further divided into I–II and III–IV stage, CDK6 amplification was significantly associated with longer DFS and OS in III-IV stage group (DFS, p = 0.036; OS, p = 0.022) rather than in I-II stage group (DFS, p = 0.776; OS, p = 0.611). On univariate and multivariate analysis of Cox hazard model, differentiation, vessel invasion, nerve invasion, invasive depth, lymph node metastasis and clinical stage were significantly associated with DFS and OS. Moreover, invasion depth was an independent factor for ESCC prognosis. Taken together, for ESCC patients in III-IV stage, CDK6 amplification indicated a better prognosis.