SKA3 is a prognostic biomarker and associated with immune infiltration in bladder cancer

Abstract

Background: Spindle and kinetochore‑associated complex subunit 3 (SKA3) has recently been considered a key regulator of carcinogenesis. However, the connection between SKA3 and immune cell infiltration remains unknown.

Methods: The current study investigated the expression mode, prognostic effect, and functional role of SKA3 in different tumors, particularly bladder cancer using numerous databases, comprising TIMER, GEPIA, HPA, UALCAN, PrognoScan, and Kaplan-Meier Plotter. Differentially expressed gene and enrichment analyses were implemented on SKA3 using R packages "edgR" and "clusterProfiler". Immunohistochemistry was further used to validate the expression of SKA3 gene in bladder cancer. Following that, the relevance of SKA3 expression to immune infiltration level in bladder cancer was evaluated using TIMER.

Results: Overall, the level of SKA3 expression in tumor tissue significantly increased than in normal tissue. In bladder cancer and other tumors, patients with high SKA3 expression levels had worse overall survival (OS) (p = 0.016), disease-specific survival (DSS) (p = 0.00004), and disease-free survival (DFS) (p = 0.032). Additionally, the major molecular functions for SKA3 included nuclear division, mitotic nuclear division, mitotic sister chromatid segregation, humoral immune response, and cell chemotaxis. Additionally, SKA3 expression was found to be positively associated with enhanced M2 macrophage and T helper (Th) 2 cell infiltration in bladder cancer.

Conclusions: Our study implies that SKA3 contributes to M2 macrophage and Th2 cell polarization by acting as an oncogene in bladder cancer. SKA3 might be a novel biomarker for evaluating prognosis and immune infiltration in bladder cancer.

Keywords: Biomarker; Bladder cancer; Immune infiltration; Prognosis; Spindle and kinetochore-associated complex subunit 3.