Correlation Between SST Methylation Status And Risk Of Digestive Tract Cancer

Background: Esophageal cancer,gastric cancer,and colorectal cancer are common digestive tract tumors in China.The incidence and the mortality rate of them are high.Three types of cancer respectively rank fifth,second and fourth in incidence and fourth,third and fifth in mortality in China.The esophagus,stomach,and colorectum all belong to the tubular digestive organs,and their tissue structures are highly similar.The development of digestive tract tumors all undergo three stages of inflammation,dysplasia,and canceration.Finding biomarkers of digestive tract tumors is an important research direction.Epigenetic regulation is a component of normal physiological regulation.DNA methylation is one of the most common epigenetic modifications.When it occurrence in the promoter region of tumor suppressor genes will inhibit gene transcription and lead to gene silencing,thereby promoting tumor development.Research had shown that promoter hypermethylation in genes,such as P16,APC,RUNX3,and CDH1,was closely related to tumorigenesis and development.Growth hormone release inhibiting hormone(Somatostatin,SST)is a member of the cyclic peptide family that has a broad inhibitory effect on the secretion of hormones.It can block the production of autocrine/paracrine growth hormones and growth factors,inhibit growth factor-mediated mitotic signals and induce apoptosis.At the same time,it can inhibit the secretion of growth hormone and growth factors,as well as anti-angiogenesis,which directly or indirectly inhibit tumorgenesis and development,make SST a potential biomarker for detecting tumor risk.In this study,the methylation status of the SST promoter region in digstive tract tumors was examined,and the effect of the methylation level of the SST promoter on the risk of digestive tract tumors was examined.At the same time,the transcription of SST in each tumor was detected to explore the effect of SST promoter methylationon on transcription.Methods: The subjects were from the First Hospital of China Medical University and Liaoning Provincial Cancer Hospitalwere patients with gastrointestinal cancer patients undergoing surgical treatment,including 50 cases of esophageal cancer(EC),99 cases of gastric cancer(GC)and 80 cases of colorectal cancer(CRC).SST promoter methylation was detected by bisulfite sequencing polymerase chain reaction(BSP).SST mRNA expression was detected by real-time quantitative PCR(q RT-PCR).The receiver operating curve(ROC)was used to evaluate the diagnostic efficacy,and the area under the curve(AUC),sensitivity(SEN),and specificity(SPE)were calculated.Results: The methylation level of SST promoter in cancer tissues of EC,GC and CRC was significantly higher than that of tumor-adjacent non-cancerous tissues(0.649±0.078 vs.0.569±0.107,p<0.05;0.622±0.09 vs.0.588±0.079,p<0.05;0.663±0.083 vs.0.617±0.042,p<0.05).Cp G site at 9,12,13,16,18,20,and 21 were the differential methylation sites in all three cancers.The methylation status of multiple Cp G sites in the tumor is related to the depth of invasion,lymph node metastasis and other biological behaviors of the tumor.The increase in the depth of invasion in the three tumors is at 14,17,18 in the esophagus,20 in the stomach,and 14 in the intestine,the methylation rate increased significantly.The expression of SST in EC tissues was lower than that in non-cancerous tissues,but with no statistical difference(p = 0.32).The expression of SST in GC and CRC tissues was significantly lower than that in non-cancerous tissues(p<0.001,p<0.001).There was no significant correlation between the methylation rate and m RNA expression of SST in EC.Except for Cp G sites 10 and 14 in GC,as well as Cp G site 10,14 and 23 in CRC,the average methylation rate and methylation rate at all other sites were significantly negatively correlated with m RNA expression(All p <0.05).The SEN,SPE and YD of multiple differential methylation sites of SST promoter in the diagnosis of digestive tract cancer were 50%,87.9%,and 0.37.Conclusion: The abnormal hypermethylation of SST promoter region is closely related to the risk of EC,GC,and CRC It may promote the occurrence and development of digest tract tumors by inhibiting gene transcription.Specific Cp G site hypermethylation combinations can be used as potential markers Risk assessment of digest tract tumors.