Comprehensive bioinformatics analysis of NCAPH expression and its clinical importance in endometrial cancer

Emerging evidence has implicated non-SMC condensin I complex subunit H (NCAPH) as a key regulator of mitosis and driver of tumorigenesis. However, its expression profiling and clinical relevance in endometrial cancer (EC) remain inadequately characterized. The present study aimed to systematically investigate the expression profiling, mutational landscape, co-expression networks and prognostic importance of NCAPH in EC through integrated bioinformatics approaches. NCAPH expression was evaluated in pan-cancer and EC cohorts derived from The Cancer Genome Atlas and Genotype Tissue Expression databases. Mutational analysis was performed using the 'maftools' package in R software. Genes co-expressed with NCAPH (with a significance threshold of P<0.05) were subjected to functional enrichment analysis using Metascape. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to evaluate the correlation between gene expression and pathway scores. The Tumor Immune Estimation Resource database was utilized to explore the correlation between NCAPH expression and the abundance of tumor-infiltrating immune cells in EC. The prognostic importance of NCAPH was assessed by Kaplan-Meier survival analysis and receiver operating characteristic curve analysis. Immunohistochemistry and western blotting was performed to validate NCAPH protein expression in clinical specimens. Results indicated that NCAPH mRNA and protein expression were significantly elevated in EC compared with normal endometrium. In addition, NCAPH expression was found to be positively correlated with advanced International Federation of Gynecology and Obstetrics stage, advanced age, TP53 mutation and aggressive histological subtypes. Somatic mutations of NCAPH occurred in 4.92% of EC cases, with missense mutations being the predominant type (79.3%). Functional enrichment analysis indicated that NCAPH-associated genes were involved in 'cell cycle', 'DNA replication' and 'oocyte meiosis'. ssGSEA exhibited a positive correlation between NCAPH and DNA repair, G₂M checkpoint, tumor cell proliferation and the PI3K/AKT/mTOR pathway. NCAPH expression exhibited a significant negative correlation with CD8+ T cell infiltration, whereas positive correlations were observed with CD4+ T helper 2 cell infiltration, CD163 and programmed death-ligand 1. In addition, high NCAPH expression was found to predict reduced 5-year overall survival and exhibited certain diagnostic efficacy (area under the curve=0.628). Overall, NCAPH may promote endometrial carcinogenesis through dysregulation of mitotic processes, induction of chromosomal instability as well as modulation of the tumor immune microenvironment and thus may serve as both a prognostic biomarker and a therapeutic target in EC.