Comprehensive Pan-Cancer Analysis of KIF18A as a Marker for Prognosis and Immunity

Abstract

KIF18A belongs to the Kinesin family, which participates in the occurrence and progression of tumors. However, few pan-cancer analyses have been performed on KIF18A to date. We used multiple public databases such as TIMER, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) to explore KIF18A mRNA expression in 33 tumors. We performed immunohistochemistry on liver cancer and pancreatic cancer tissues and corresponding normal tissues to examine the expression of KIF18A protein. Univariate Cox regression and Kaplan–Meier survival analysis were applied to detect the effect of KIF18A on overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) of patients with these tumors. Subsequently, we explored KIF18A gene alterations in different tumor tissues using cBioPortal. The relationship between KIF18A and clinical characteristics, tumor microenvironment (TME), immune regulatory genes, immune checkpoints, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repairs (MMRs), DNA methylation, RNA methylation, and drug sensitivity was applied for further study using the R language. Gene Set Enrichment Analysis (GSEA) was utilized to explore the molecular mechanism of KIF18A. Bioinformatic analysis and immunohistochemical experiments confirmed that KIF18A was up-regulated in 27 tumors and was correlated with the T stage, N stage, pathological stage, histological grade, and Ki-67 index in many cancers. The overexpression of KIF18A had poor OS, DSS, and PFI in adrenocortical carcinoma (ACC), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower-grade glioma (LGG), liver cancer (LIHC), lung adenocarcinoma (LUAD), and pancreatic cancer (PAAD). Univariate and multivariate regression analysis confirmed KIF18A as an independent prognostic factor for LIHC and PAAD. The mutation frequency of KIF18A is the highest in endometrial cancer. KIF18A expression levels were positively associated with immunocyte infiltration, immune regulatory genes, immune checkpoints, TMB, MSI, MMRs, DNA methylation, RNA methylation, and drug sensitivity in certain cancers. In addition, we discovered that KIF18A participated in the cell cycle at the single-cell level and GSEA analysis for most cancers. These findings suggested that KIF18A could be regarded as a latent prognostic marker and a new target for cancer immunological therapy.