Integrated Profiling Delineated KIF18A as a Significant Biomarker Associated with Both Prognostic Outcomes and Immune Response in Pancreatic Cancer.

Abstract

Purpose: Kinesin family member 18A (KIF18A) is a member of the kinesin-8 family of motor proteins, involved in the progression and metastasis of various tumors. However, its role in pancreatic adenocarcinoma (PAAD) remains unclear.

Methods: To evaluate that role, RNA sequencing datasets, complemented by pertinent clinical metadata, were procured from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) repositories. The protein expression level of KIF18A in PAAD was derived from human protein atlas (HPA) database. The differences in KIF18A expression levels and prognostic related genes were identified through multivariate Cox regression and Lasso regression analysis to construct a prognostic risk model. The Tumor Mutation Burden (TMB), Microsatellite (MSI), immune landscape, mutation landscape and drug sensitivity of high- and low-expression KIF18A groups were assessed in immunotherapy cohorts and KIF18A expression cohorts. Finally, in vitro experiments were conducted to elucidate the molecular function of KIF18A in regulating the malignant behavior of PAAD.

Results: KIF18A is highly expressed in PAAD and is closely related to worse clinical stage and poor prognosis. Single cell analysis revealed that KIF18A is mainly expressed in microtubules of tumor cells and participated in mitosis and cell cycle of PAAD. Further analysis revealed that the expression of KIF18A is closely related to TMB, MSI, and immune cell infiltration. In vitro experiments confirmed that KIF18A promotes the proliferation, migration and expression of adhesion molecules in PAAD, and inhibits angiogenesis. In addition, the high expression of KIF18A is positively related to ferroptosis and m6A genes expression, and its high expression is driven by mutated KRAS and TP53.

Conclusion: This study confirmed that KIF18A can be used as a marker to predict the prognosis and immunotherapy of PAAD, and it participates in the formation of microtubules in PAAD cells and promotes the malignant behavior of PAAD.