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.
Keywords: IMPDH1; hepatocellular carcinoma (HCC); immunotherapy; m-6-A; methylation; pan-cancer; tumor immune microenvironment.
Copyright © 2022 Liu, Zhang, Zhou and Liu.