IMPDH1, a prognostic biomarker and immunotherapy target that correlates with tumor immune microenvironment in pan-cancer and hepatocellular carcinoma

Backgrounds IMPDH1, a rate-limiting enzyme in de novos synthesis of guanine nucleotides, plays an essential role in the growth and progression of certain tumors. However, there is still a lack of study on IMPDH1 evaluating its role in the tumor immune microenvironment, the potential mechanisms, and its potential as a promising tumor therapeutic target. Methods The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), TIMER2.0, KM-Plotter, University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), cbioportal, The Human Protein Atlas (HPA), and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) were used to perform the systematic analysis of IMPDH1, including mRNA expression, protein expression, prognostic value, Enrichment analysis, DNA methylation, immune cell infiltration in pan-cancer, Then, we conducted qRT-PCR and immunohistochemistry to analyze the expression level of IMPDH1 in cancer tissues and non-cancer tissues of patients with primary hepatocellular carcinoma (HCC), and performed the same verification at cellular level. Results We discovered that IMPDH1 was highly expressed in a variety of tumors and was associated with poor prognosis. IMPDH1 not only had the potential as a tumor prognostic marker and therapeutic target, but also was closely related to immune cells, immune checkpoints and immune-related genes and pathways in the tumor immune microenvironment (TIME). Meanwhile, IMPDH1 expression influenced the efficacy and prognosis of tumor patients treated with immune checkpoint inhibitors. Conclusions IMPDH1 may be as a potential combined target of immunotherapy.