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

## TL;DR

High KIFC1 levels in kidney cancer are linked to worse survival, aggressive tumor features, and immune response, suggesting it could be a new target for treatment.

## Contribution

This study identifies KIFC1 as a novel prognostic biomarker and potential therapeutic target in clear cell renal cell carcinoma.

## Key findings

- High KIFC1 expression correlates with poor survival and advanced tumor stage in clear cell renal cell carcinoma.
- KIFC1 is linked to immune response pathways and resistance to targeted therapies in kidney cancer.
- KIFC1 is associated with sarcomatoid differentiation and epithelial–mesenchymal transition in ccRCC.

## Abstract

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.

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.

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.

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.