Kinesin-related genes stratified the prognosis and immune responses of clear cell renal cell carcinoma.

BACKGROUND

Clear cell renal cell carcinoma (ccRCC) is a prevalent and aggressive form of kidney cancer. Recently, the identification of suitable subtypes in ccRCC for the prediction of prognosis and immune infiltration remains limited. Kinesin superfamily proteins (KIFs), a group of molecular motor proteins, have been found to play crucial roles in tumor progression and patient prognosis in various cancers. However, the subtypes in ccRCC based on KIFs remain poorly understood.

METHODS

In this study, transcriptional profiles of ccRCC were analyzed using data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Differential expression of KIFs was identified using R software. Subsequently, ccRCC patients were stratified into two distinct subgroups based on non-negative matrix factorization (NMF) analysis. Comparative analyses were performed to evaluate prognosis, mutations, and immune cell infiltration between these subtypes. Furthermore, signature genes associated with the identified subtypes were determined, followed by an investigation into their relationship with clinical characteristics and response to immune checkpoint inhibitors. Validation studies involving immunohistochemical staining, malignant phenotype assays, and immunofluorescence were conducted to assess the expression and function of these signature genes.

RESULTS

Five KIFs genes, namely, KIF21B, KIF18B, KIF20A, KIF4A, and KIF13B, were identified as classifiers for categorizing ccRCC patients into two distinct subtypes known as KPCS1 and KPCS2. The aggressive subtype, KPCS2, was found to be associated with poorer survival outcomes. Furthermore, higher immune infiltration and copy number variations were observed in the KPCS2 subtype. Four signature genes (SLCA15, WDR72, PSAT1, and HJURP) displayed significant correlations with clinical characteristics and were determined to be linked to the ccRCC subtypes. The expression patterns and functional roles of these signature genes were subsequently validated in both ccRCC cells and tissues.

CONCLUSION

KIFs-associated subtypes provide valuable insights into the molecular characteristics and prognostic implications of ccRCC, thereby suggesting potential therapeutic targets for intervention.