Bioinformatics-guided analysis uncovers TIGIT as an epigenetically regulated immunomodulator affecting immunotherapeutic sensitivity of gastric cancer.

Background Immunomodulatory genes play significant roles in the regulation of immunological properties of gastric cancer, but the effect of epigenetic regulation of these genes on the immune properties is unknown. Method I analyzed the methylation-expression correlation among all immunomodulators and compared with the non-immunomodulators. The association between epigenetically regulated immunomodulators (ERI) and tumor microenvironment is evaluated. A key immunomodulator TIGIT is further selected to investigate the potential value in the regulation of immunologic properties. Furthermore, the prognostic value and the immunotherapeutic potential of TIGIT are also explored. Result Four genes are identified as ERIs based on the negative correlation between expression and methylation. Association analysis shows that three ERIs participate in the regulation of the immune microenvironment of gastric cancer. Among these ERIs, TIGIT is identified as a key immunomodulator. TIGIT is found to be significantly associated with immune properties. The high TIGIT expression group tends to display an active immune landscape. TIGIT expression is also found to be associated with survival and immunotherapeutic sensitivity. High TIGIT expression group has a favorable prognosis and is more likely to respond to immunotherapy than the low expression group. Conclusion TIGIT is an epigenetically regulated immunomodulator of gastric cancer which can modify the immune activity and affect immunotherapeutic sensitivity. These findings can promote the research of epigenetic therapies and improve the survival of cancer patients by sensitizing tumors to immune therapies.