A comprehensive expression profiles and prognostic values analysis of inosine 5'-monophosphate dehydrogenase type II (IMPDH2) in human tumors Running title: A pan-cancer analysis of IMPDH2

Background: Inosine 5'-monophosphate dehydrogenase type II (IMPDH2) was thought to be involved in cancer initiation, progression, and treatment, but its biological role and underlying mechanism in pan-cancers are not fully studied. Our goal was to systematically investigate expression status and prognostic value through online data mining. Methods The expression and prognostic value of IMPDH2 in pan-cancer were analyzed using the HPA, GEPIA, TIMER, UALCAN, PrognoScan, Kaplan–Meier Plotter and DriverDBv3, and confirmed by immunohistochemical staining in gastric cancer. Function analysis was determined with GeneMANIA, STRING, and Metascape interactive tools, and alterations were examined by cBioPortal and UCSC Xena. Moreover, TISIDB and TIMER were applied to explore the relationships between IMPDH2 expression and immune infiltration, subtypes. Results Upregulation of IMPDH2 was observed in multiple human cancer tissues and relevant to a poor survival. Interactive analysis indicated that IMPDH2 was significantly associated with the metabolism of nucleotides, nucleobase metabolic process and regulation of canonical Wnt signaling pathway. Notably, a heatmap revealed positive correlations of IMPDH2 expression with macrophage M2, common lymphoid progenitor, myeloid derived suppressor cells, and negative correlations with macrophage M1, T cell follicular helper, B cell, T cell CD8+, dendritic cell. Additionally, there was a significant association between the IMPDH2 copy number, DNA methylation, exon expression levels and disease-free interval. Conclusions Together, IMPDH2 could act as a novel biomarker for the prognostic and immunological role in multiple human cancers.