Abstract
BackgroundAbnormal methylation of TNFRSF10C was found to be associated with different types of cancers, excluding colorectal cancer (CRC). In this paper, the performance of TNFRSF10C methylation in CRC was studied in two stages.MethodThe discovery stage was involved with 38 pairs of CRC tumor and paired adjacent non-tumor tissues, and 69 pairs of CRC tumor and paired adjacent non-tumor tissues were used for the validation stage. Quantitative methylation specific PCR (qMSP) method and percentage of methylated reference (PMR) were used to test and represent the methylation level of TNFRSF10C, respectively. A dual-luciferase reporter gene experiment was conducted to evaluate the promoter activity of TNFRSF10C fragment.ResultsA significant association of TNFRSF10C promoter hypermethylation with CRC was found and validated (discovery stage: 24.67 ± 7.52 vs. 3.36 ± 0.89; P = 0.003; validation stage: 31.21 ± 12.48 vs. 4.52 ± 1.47; P = 0.0005). Subsequent analyses of TCGA data among 46 pairs of CRC samples further confirmed our findings (cg23965061: P = 4E − 6; cg14015044: P = 1E − 7). Dual-luciferase reporter gene assay revealed that TNFRSF10C fragment was able to significantly promote gene expression (Fold change = 2.375, P = 0.013). Our data confirmed that TNFRSF10C promoter hypermethylation can predict shorter overall survival of CRC patients (P = 0.032). Additionally, bioinformatics analyses indicated that TNFRSF10C hypermethylation was significantly associated with lower TNFRSF10C expression.ConclusionOur work suggested that TNFRSF10C hypermethylation was significantly associated with the risk of CRC.
Highlights
Colorectal cancer (CRC) is the third most common cancer and the fourth most universal cause of cancer-related death around the world (Ferlay et al, 2015)
We recruited 107 colorectal cancer (CRC) patients to study the relationship between TNFRSF10C methylation and CRC (Table 1)
We explored the association between TNFRSF10C methylation and CRC in the Chinese population
Summary
Colorectal cancer (CRC) is the third most common cancer and the fourth most universal cause of cancer-related death around the world (Ferlay et al, 2015). DNA methylation is one of the important epigenetic modification mechanisms (Dawson & Kouzarides, 2012), and it has been verified to be associated with CRC (Capuano et al, 2015). Abnormal methylation of TNFRSF10C was found to be associated with different types of cancers, excluding colorectal cancer (CRC). A significant association of TNFRSF10C promoter hypermethylation with CRC was found and validated (discovery stage: 24.67 ± 7.52 vs 3.36 ± 0.89; P = 0.003; validation stage: 31.21 ± 12.48 vs 4.52 ± 1.47; P = 0.0005). Dual-luciferase reporter gene assay revealed that TNFRSF10C fragment was able to significantly promote gene expression (Fold change = 2.375, P = 0.013). Our data confirmed that TNFRSF10C promoter hypermethylation can predict shorter overall survival of CRC patients (P = 0.032). Our work suggested that TNFRSF10C hypermethylation was significantly associated with the risk of CRC
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