Abstract

Aberrant activation of SHH signaling contributes to the progression of multiple malignancies, with KIF7 functioning as a critical mediator that regulates signal transduction from SMO to GLI transcription factors. However, the specific role of KIF7 in ccRCC has not been fully elucidated. In this study, we investigated the expression pattern, prognostic significance, functional role, and potential mechanisms of KIF7 in ccRCC. Analysis of TCGA-KIRC data demonstrated that KIF7 expression was significantly elevated in tumor tissues compared with adjacent normal tissues. High KIF7 expression was strongly associated with advanced pathological stage and poor overall survival. IHC performed on commercial tissue microarrays further confirmed increased KIF7 protein levels in ccRCC samples. Functional experiments in the 786-O cell line revealed that KIF7 overexpression markedly enhanced cell proliferation. Mechanistically, KIF7 overexpression activated the Wnt/β-catenin signaling pathway and upregulated downstream cell cycle regulators, including c-Myc and c-Jun. KIF7 expression was positively correlated with infiltration of CD4 + T cells, macrophages, and neutrophils. Moreover, it showed significant positive associations with immune checkpoint molecules PDCD1 and CD160. GSCA/GDSC-based drug sensitivity prediction suggested that high KIF7 expression was associated with increased predicted sensitivity to docetaxel and bleomycin, whereas no significant association was observed for I-BET-762. In conclusion, KIF7 plays a tumor-promoting role in ccRCC by enhancing proliferation, activating Wnt/β-catenin signaling. Additionally, it was associated with shaping the immune microenvironment. These findings highlight KIF7 as a potential prognostic biomarker and therapeutic target in ccRCC.