Pan-cancer analysis, providing a reliable basis for IDO2 as a prognostic biomarker and target for immunotherapy

Objectives: Indoleamine 2,3-dioxygenase 2 (IDO2) is a homologous protein of the classical immune negative regulator Indoleamine 2,3-dioxygenase 1 (IDO1) that is indispensable in the metabolism of tryptophan and is closely related to the pathogenesis and progression of tumors. Nevertheless, the mechanism of IDO2 in malignant tumors is not fully understood warranting further research.Methods: Data related to IDO2 in pan-cancer was obtained from The Cancer Genome Atlas (TCGA) database. Differences in IDO2 expression between pan-cancerous and corresponding normal tissues were analyzed, and survival rates were analyzed using Kaplan-Meier. The correlation between IDO2 expression and tumor-infiltrating immune cells (TIICs), tumor mutational load (TMB), microsatellite instability (MSI), mismatch repair (MMR), immune checkpoints (ICP) and DNA methyltransferase (DNMT) was investigated by Spearman correlation analysis. Functional enrichment analysis of IDO2 was performed to explore its biological and molecular roles in tumors.Results: Our comprehensive pan-cancer analysis showed that IDO2 expression was significantly altered in most malignancies and correlated with poor prognosis. The expression of IDO2 was strongly associated with the progression of several tumors and excessive infiltration of immune cells in the tumor microenvironment (TME). The expression of IDO2 significantly correlated with TMB, MSI, MMR and ICP in different tumors. More importantly, functional enrichment analysis showed that IDO2 acts primarily through the regulation of antitumor immunological processes. RT-PCR validated IDO2 expression in multiple cancer cell lines, consistent with the bioinformatic analysis results.Conclusions: IDO2 is closely related to tumor genesis and immunity, and can be used as an adjunct for the diagnosis and prognosis assessment of many tumors.