KIF4A functions as a diagnostic and prognostic biomarker and regulates tumor immune microenvironment in skin cutaneous melanoma

PATHOLOGY RESEARCH AND PRACTICE(2024)

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摘要
Background: KIF4A is upregulated in various malignancies and serves as an independent risk factor. However, its function in skin cutaneous melanoma (SKCM) and the regulation of the immunological environment remains unknown. Methods: We first explored the mRNA and protein levels of KIF4A in SKCM through public databases. Then, the co-expressed genes with KIF4A in SKCM and their functional enrichment analysis were performed. Moreover, the clinical value, relationship with immune infiltration and tumor microenvironment (TME), as well as the correlation between KIF4A and immunomodulators were evaluated. In addition, we validated the function of KIF4A by in vitro experiments such as CCK-8 assay, clone formation and wound healing assay. Results: Our data reveal that the mRNA and protein levels of KIF4A are highly expressed in SKCM. Moreover, functional enrichment analysis of the top 50 co-expressed genes with KIF4A showed significant association with organelle fission, tubulin binding and immune processes. KIF4A can distinguish SKCM from normal tissue and predict a poorer prognosis. A negative association was observed between KIF4A and TME, and KIF4A exhibited a negative correlation with most immunomodulators. Additionally, the knockdown of KIF4A inhibited the proliferation and migration ability of A375 cells. Conclusions: Our findings suggest that KIF4A promotes the progression of SKCM and is negatively associated with immune infiltration and immunomodulators, which indicates a poor prognosis.
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关键词
Skin cutaneous melanoma (SKCM),KIF4A,Biomarker,Tumor microenvironment (TME)
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