KIFC1 is Associated With Sarcomatoid Differentiation, Immune Response, and a Poor Prognosis in Clear Cell Renal Cell Carcinoma

INTRODUCTION: Centrosome clustering is a cancer-specific adaptation that allows cells with centrosome amplification to evade mitotic catastrophe and has emerged as a potential therapeutic target. We analyzed the prognostic role of several molecules related to centrosome clustering and found that Kinesin Family Member C1 (KIFC1) was strongly associated with a poor prognosis. KIFC1, a kinesin motor protein, plays a central role in centrosome clustering. However, its biological and clinical significance in clear cell renal cell carcinoma (ccRCC) remains poorly understood. METHODS: We conducted a comprehensive analysis using several public datasets (TCGA KIRC, JAVELIN101, IMmotion151, and others) and a Hiroshima ccRCC cohort (n = 110) to evaluate the expression of KIFC1, clinicopathological associations, the prognosis, and treatment response. Gene Set Enrichment Analysis was performed to explore associated pathways. RESULTS: Immunohistochemical and in silico analyses showed that high KIFC1 expression was significantly associated with high tumor grade, advanced TNM stage, and sarcomatoid differentiation. A multivariate analysis demonstrated that the high-expression of KIFC1 was independently associated with poor overall survival. Gene Set Enrichment Analysis revealed enrichment of epithelial-mesenchymal transition and interferon gamma response pathways in KIFC1-high tumors. The expression of KIFC1 was also correlated with TKI resistance, immune response, high clonal neoantigen load, and BAP1 mutation. CONCLUSION: KIFC1 serves as a multifunctional molecule linking epithelial-mesenchymal transition, immune modulation, and treatment resistance. It may be a promising prognostic biomarker and therapeutic target in ccRCC, warranting further functional and clinical investigation.