Exploring the prognostic role and expression patterns of FAM3A family genes in kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) is the most common subtype of kidney cancer, characterized by complex molecular alterations. The FAM3 gene family, comprising FAM3A, FAM3B, FAM3C, and FAM3D, has been implicated in various cancers, but their roles in KIRC are not well understood. This study investigated the expression, diagnostic potential, and functional significance of FAM3 family genes in KIRC. This study explores the expression and functional roles of FAM3 family genes in KIRC using in silico and in vitro experiments. We performed RT-qPCR analysis to assess the expression of FAM3A, FAM3B, FAM3C, and FAM3D in KIRC and normal cell lines, revealing significant upregulation of FAM3A and FAM3D and downregulation of FAM3B and FAM3C in cancerous cells. ROC analysis demonstrated that FAM3 genes possess high diagnostic potential. Further validation using TCGA, OncoDB, and Human Protein Atlas (HPA) databases confirmed these expression patterns and their association with cancer progression. Methylation analysis indicated hypomethylation of FAM3A and FAM3D and hypermethylation of FAM3B and FAM3C, correlating with differential gene expression. Survival analysis revealed that high FAM3A expression was linked to poor prognosis, while low FAM3C expression correlated with reduced survival. Functional assays demonstrated that knockdown of FAM3A in 786-O cells reduced proliferation, clonogenicity, and migration, underscoring its potential role in KIRC pathogenesis. Additionally, FAM3 genes exhibited significant correlations with immune cell infiltration, immune inhibitor genes, and drug resistance, suggesting their involvement in modulating the tumor microenvironment. The miRNA-mRNA network analysis identified hsa-mir-19b-3p as a key regulator of FAM3 genes, further implicating these genes in KIRC progression. This comprehensive analysis highlights the potential of FAM3 genes as biomarkers and therapeutic targets in KIRC.