Site-specific Methylation of SST Gene May Serve as a Biomarker for Risk Prediction of Gastrointestinal Tract Cancers as Well as Promoting Malignant Behavior by Regulating Gene Expression

Background: DNA methylation plays an important role in the regulation of gene expression as well as the occurrence and development of cancer. Abnormal hypermethylation in the promoter region of tumor suppressor genes is a recognized molecular events related to carcinogenesis. Somatostatin (SST) is considered as a tumor suppressor gene. The study aims to explore the relationship between the promoter methylation status of SST and the risk of gastrointestinal tract cancers and further to evaluate its diagnostic value.Methods: Tissue samples were used for DNA isolation and RNA isolation. SST methylation was detected by biosulfite sequencing PCR, and SST mRNA expression was detected by quantitative real-time reverse transcription-polymerase chain reaction. The receiver operating curve (ROC) was drawn to evaluate the efficacy of SST CpG methylation on the diagnosis of digestive tract tumors by calculating the sensitivity, specificity and Youden index.Results: The methylation level of SST promoter in cancer tissue were significantly increased compared with adjacent control tissue (EC: 0.649 ± 0.078 vs. 0.569 ± 0.107, p <0.05, GC: 0.622 ± 0.09 vs. 0.588 ± 0.079, p <0.05, CC : 0.663 ± 0.083 vs. 0.617 ± 0.042 p <0.05). Significantly different methylation sites contained CpG +18, +25, +44, +94, +100, +127, and +129. SST methylation status was associated with clinical phenotypes such as lymph node metastasis and vascular tumor thrombus. CpG sites in two tumors (+85 in EC, +94 in CC) were positively correlated with the depth of infiltration. The expression level of SST in gastric and colorectal cancer tissue was significantly lower than that in adjacent control tissue (both p <0.001). However, no statistically significant difference was found in EC group (p = 0.32). Except CpG +25 and +85 sites in GC and the +25, +85 and +148 sites in CRC, the methylation rate of each CpG was negatively correlated with gene expression (all P <0.05). Combined detection of eight CpG sites methylation (+18,+42,+44,+85,+92,+94,+129 and+138) showed the best area under the curve of 0.817 with sensitivity of 76.5% and specificity of 75%.Conclusions: Abnormal hypermethylation in SST promoter region increased the risk of gastrointestinal tract tumors, as well as promoting cancer progression by regulating gene expression. SST methylation status may serve as site-specific biomarker for risk prediction of gastrointestinal tract tumors.