Springer Netherlands

Integrative genomic and functional characterization of FAM3 family genes reveals their diagnostic and prognostic roles in kidney renal clear cell carcinoma - Cytotechnology

This study comprehensively investigated the role of FAM3 family genes (FAM3A, FAM3B, FAM3C, and FAM3D) in Kidney Renal Clear Cell Carcinoma (KIRC) using an integrative multi-dimensional approach. Analyses included mRNA expression profiling, promoter methylation assessment, genetic alteration evaluation, prognostic modeling, immune and molecular subtype correlations, gene enrichment analysis, in vitro functional validation, and drug sensitivity evaluation based on TCGA datasets and experimental data. Expression analysis revealed significant upregulation of FAM3A and FAM3D and downregulation of FAM3B and FAM3C in KIRC tissues compared with normal kidney samples. ROC curve analysis demonstrated their diagnostic potential. Promoter methylation analysis indicated hypomethylation of FAM3A and FAM3D and hypermethylation of FAM3B and FAM3C, consistent with their expression profiles. Minimal genetic alterations were observed, suggesting that epigenetic regulation may primarily contribute to their dysregulation. Prognostic modeling associated FAM3 gene expression with overall survival, indicating their potential as predictive biomarkers. Immune infiltration and subtype analyses suggested that FAM3 genes are involved in the modulation of the tumor microenvironment. Functional validation demonstrated that knockdown of FAM3A and FAM3D suppressed cell proliferation and colony formation, while enhancing migratory and wound-healing abilities in KIRC cell lines. Drug sensitivity analysis identified correlations between FAM3 expression and responsiveness to anticancer compounds. These findings highlight the diagnostic, prognostic, and therapeutic significance of FAM3 family genes in KIRC, providing valuable insights for future clinical translation and potential targeted therapy development.