Bioinformatic profiling of human KIF genes: Unravelling key regulators of breast tumour growth

In breast cancer, the abnormal expression of certain kinesins facilitates tumour development, chromosomal instability, and metastasis. Identifying the chief kinesins involved in breast cancer progression would be advantageous in evaluating their role as biomarkers. Consequently, our research seeks to examine the function of kinesins in breast carcinogenesis. Gene expression omnibus (GEO) database was used to identify differentially expressed kinesins in breast cancer patients, considering p < 0.05 and fold change (|log FC| > 0.5) statistically significant. The findings were validated using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) tool, and prognostically significant kinesins were selected. The Protein-protein interaction network (PPIN) was constructed using STRING to identify the hub gene network, which was then subjected to gene ontology and pathway enrichment analysis. The genetic and epigenetic anomalies of the identified kinesins were evaluated using METABRIC data and MethSurv, respectively. Finally, the immunomodulatory role of kinesins was investigated using the web-based tool TIMER. We identified KIF2C, KIF4A, and KIF11 to be prognostically significant kinesins involved in breast carcinogenesis. All three identified kinesins were significantly upregulated in breast cancer cases, and their elevated expression exhibited poor survival of the patients. In the METABRIC database, KIF4A exhibited mutations in 5% of the breast cancer cases, whereas KIF2C and KIF11 were mutated in 4% and 3% of cases, respectively. The CpG islands in the promoter regions of KIF2C, KIF4A, and KIF11 were meticulously investigated for epigenetic alterations; cg20487572, cg27286863, and cg18863837 exhibited the most substantial impact on patient survival. The hub genes, including the discovered kinesins, demonstrated a significant function in the mitotic pathway, and disease enrichment analysis indicated their strong relationship with breast carcinoma. Moreover, all three kinesins had a positive connection with neutrophil levels, indicating a significant function in the immunomodulation of the tumour microenvironment. Our study identified KIF2C, KIF4A, and KIF11 as essential kinesins in the advancement of breast cancer. Additionally, research on breast cancer patients and in vitro investigations to examine the functional roles of the discovered kinesins will enhance the understanding of their involvement in breast carcinogenesis.