Identification of genomic biomarkers associated with the clinicopathological parameters and prognosis of esophageal squamous cell carcinoma

鉴定与食管鳞状细胞癌临床病理参数和预后相关的基因组生物标志物

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Abstract

BACKGROUND: At present no objective prognostic biomarkers have been established in esophageal squamous cell carcinoma (ESCC). OBJECTIVE: To identify the genomic biomarkers associated with clinicopathological factors and prognosis of ESCCs. METHODS: Real-time PCR was used to analyze the copy number change and mRNA expression of genes. The survival curves were plotted according to Kaplan-Meier method and checked by log-rank test. RESULTS: We revealed the copy number increase of CACNA1C (12p13.33) and MRPL21 (11q13.2) as well as decrease of VIPR2 (7q36.3) and MAP3K7 (6q15) in ESCC by Real-time PCR, and also found that MRPL21 was significantly overexpressed and VIPR2 was underexpressed in ESCC. Gain of CACNA1C was significantly associated with differentiation (P = 0.043), and loss of VIPR2 was significantly linked with good prognosis (P = 0.016). Most importantly, we revealed that loss of MAP3K7 was significantly correlated with good prognosis in ESCC patients (n = 159, P = 0.004), especially in Grade II and pN0 patients (n = 76, P = 0.005 and n = 74, P = 0.024). Multivariate analysis confirmed that MAP3K7 loss provided prognostic information in ESCC (HR, 0.454; 95% CI: 0.208-0.995; P = 0.048). CONCLUSIONS: Loss of MAP3K7 may be a candidate prognostic factor in ESCC.

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