We should pay more attention to the complexity of the intrinsic entanglement between GPSM2 and HCC

Abstract Overexpression of G-protein signaling modulator 2 (GPSM2) is a common feature of many cancers, however, detailed research regarding the role of GPSM2 in the immune microenvironment of hepatocellular carcinoma (HCC) is lacking. In this study, databases were utilized to analyze the expression, the relationship between GPSM2 and immune infiltration, and the effect of GPSM2 on the prognosis of patients with HCC. The results show that GPSM2 was associated with oncogenes KRAS, FGFR2, PI3KCA, and AKT1, as well as with CDK1/2/4 and E2F1, which are enriched in the cell cycle. A positive correlation with apoptosis inhibitory protein BCL2, AASDH, GLIS2, GNAI1, GNAI2, NUMA1, and GNAO1 was observed, along with CTLA4, CD274, HAVCR2, LAG3, PDCD1, PDCD1LG2, TIGIT, SIGLEC15, and PSMG1. Alterations in copy number and DNA methylation levels could be the underlying mechanisms responsible for GPSM2 regulation. has-miR-22-3p might be the most potential regulatory miRNA of GPSM2, and BX284668.6, LINC00858, and MIR4435-2HG might be the three most upstream lncRNAs of the has-miR-22-3p/GPSM2 axis in HCC. In summary, GPSM2 affects the tumor immune microenvironment, and targeting GPSM2 might increase the efficacy of immunotherapy in HCC. Alterations in copy number and DNA methylation levels could be the underlying mechanisms responsible for GPSM2 upregulation.