Pan-Cancer Analysis Revealed ITM2A as a Predictive Biomarker of Prognosis and Immunotherapy for Kidney Renal Clear Cell Carcinoma

Abstract

Abstract Immunotherapies including the use of immune-checkpoint inhibitors or adoptive cellular transfer have revolutionized the efficacy of various malignancies. However, the identification of potential markers in pan-cancer and the underlying molecular mechanisms in the tumor microenvironment (TME) remain unclear. We evaluated the association of potential T-cell driver genes (TDGs) reported previously with pan-cancer and identified ITM2A was under-expressed in multiple cancers, suggesting a worse prognosis in Acute Myeloid Leukemia (LAML), Skin Cutaneous Melanoma (SKCM), Liver hepatocellular carcinoma (LIHC), Kidney renal clear cell carcinoma (KIRC), and Pancreatic adenocarcinoma (PAAD). Results of the single-cell analysis showed that ITM2A was significantly concentrated in T cells. Patients with low ITM2A had a worse prognosis, higher tumor stage, and grade, which could be an independent prognostic risk factor in KIRC. The abnormal regulation of ITM2A in KIRC was confirmed by immunohistochemistry. Further research suggested that ITM2A was positively correlated with immunomodulators, TIICs, immune checkpoints, TMB, and immune score in KIRC. The aberrant expression of ITM2A could predict the immunotherapy response of ICB in KIRC. In conclusion, as a driver gene of T cells, ITM2A may be a potential prognostic and immunological characteristic for KIRC.