Correlations of Promoter Methylation in WIF-1, RASSF1A, and CDH13 Genes with the Risk and Prognosis of Esophageal Cancer
Qiang Guo, Hai-Bo Wang, Yong-Hui Li, He-Fei Li, Ting-Ting Li, Wen-Xue Zhang, Sha-Sha Xiang, Zhen-Qing Sun
Department of Thoracic Surgery, The Affiliated Hospital of Hebei University, Baoding, Hebei, China (mainland)
Med Sci Monit 2016; 22:2816-2824
Available online: 2016-08-10
This study was designed to explore the correlations of promoter methylation in Wnt inhibitory factor-1 (WIF-1), ras-association domain family member 1A (RASSF1A), and Cadherin 13 (CDH13) genes with the risk and prognosis of esophageal cancer (EC).
MATERIAL AND METHODS: A total of 71 EC tissues from resection and 35 adjacent normal tissues were collected. Methylation status in the promoter region was detected by methylation- and non-methylation-specific primers. Corresponding mRNA levels were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Correlations between the methylations of these 3 genes and clinicopathologic characteristics were analyzed. Kaplan-Meier method and Cox regression model were used to investigate the relationships between WIF-1, RASSF1A, and CDH13 promoter methylations and the prognosis of EC.
RESULTS: Compared with adjacent normal tissues, the methylation frequencies of WIF-1, RASSF1A, and CDH13 genes were significantly higher but the mRNA levels of these 3 genes were significantly lower in EC tissues (all P<0.05). WIF-1 and CDH13 promoter methylations were associated with the degree of tumor differentiation and WIF-1 and RASSF1A promoter methylations were associated with age (all P<0.05). The survival rates of patients with WIF-1, RASSF1A, and CDH13 methylations were significantly lower than those of patients without methylation (all P<0.05). WIF-1, RASSF1A, and CDH13 promoter methylations were independent risk factors affecting the prognosis of EC (all P<0.05).
CONCLUSIONS: WIF-1, RASSF1A, and CDH13 promoter methylations are associated with EC. The methylation levels are negatively related with the prognosis in EC.
Keywords: Adaptor Proteins, Signal Transducing - metabolism, Adult, Cadherins - metabolism, DNA Methylation, Esophageal Neoplasms - genetics, Genetic Predisposition to Disease, Prognosis, Promoter Regions, Genetic, Repressor Proteins - metabolism, Risk Factors, Tumor Suppressor Proteins - metabolism