Expression characteristics, immune signatures, and prognostic value of the KIF family members identified across cancers

Abstract

Aim: The overexpression of Kinesin superfamily proteins (KIFs) has been increasingly recognized as a critical factor associated with unfavorable prognostic outcomes across a spectrum of cancers. This study aims to elucidate the multifaceted role of KIFs within the tumor immune microenvironment and explore their potential as targets for precision cancer therapy.

Methods: Utilizing comprehensive genomic datasets from the Cancer Genome Atlas and Genotype-Tissue Expression databases, we systematically analyzed KIF expression patterns and their potential oncogenic functions. To investigate the functional impact of KIF3A in hepatocellular carcinoma (HCC), we synthesized siKIF3A and transfected it into HepG2 cells, followed by a series of functional assays. Cell proliferation was meticulously evaluated using EdU incorporation, CCK8, and colony formation assays, while cell migration was assessed through scratch wound healing and Transwell migration assays. Quantitative analysis of gene and protein expression levels was performed using RT-PCR and Western blot techniques, respectively.

Results: Our findings reveal that KIFs exhibit remarkably high mutation frequencies across multiple cancer types. Furthermore, we identified significant genomic and epigenetic modifications of KIFs in various tumors, with specific oncogenic mutations in certain cancers potentially serving as regulatory mechanisms for KIFs expression. Notably, tumor-derived KIFs demonstrate a strong association with immune cell infiltration patterns, suggesting their potential as novel therapeutic targets in cancer immunotherapy. Importantly, the majority of KIF family genes show significant correlations with patient prognosis, underscoring their clinical relevance. Specifically, KIF3A emerges as a promising prognostic marker for HCC, demonstrating significantly higher expression levels in HCC tissues compared to adjacent non-cancerous tissues (P < 0.05). This overexpression strongly correlates with poor survival outcomes and established risk factors. Functional studies reveal that knockdown of KIF3A significantly inhibits the proliferation and migration capabilities of HCC cells (P < 0.05), highlighting its critical role in tumor progression. Our findings suggest that KIF3A not only serves as a valuable prognostic biomarker but also represents a potential therapeutic target for HCC patients, particularly through its involvement in tumor immune regulation mechanisms.

Conclusion: This comprehensive study provides novel insights into the role of KIFs, particularly KIF3A, in cancer biology and offers promising avenues for the development of targeted therapies in hepatocellular carcinoma. The integration of genomic analysis with functional validation underscores the potential of KIFs as both diagnostic markers and therapeutic targets in cancer management.

Keywords

KIFs / pan-cancer / hepatocellular carcinoma / immunoinfiltration / proliferation / migration

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