Muhammad Shoaib, Yan Pengyu, Wang Huifang, Mahmood Ahmad, Naqvi Syed Shah Zaman Haider, Zaeem Muhammad, Liu Chun
Department of Urology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China.
Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Ürümqi, 830054, China.
Sci Rep. 2025 Jul 1;15(1):22397. doi: 10.1038/s41598-025-05658-x.
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.
肾透明细胞癌（KIRC）是最常见的肾癌亚型，其特征是复杂的分子改变。FAM3基因家族由FAM3A、FAM3B、FAM3C和FAM3D组成，已被证明与多种癌症有关，但其在KIRC中的作用尚不清楚。本研究调查了FAM3家族基因在KIRC中的表达、诊断潜力和功能意义。本研究通过计算机模拟和体外实验探索了FAM3家族基因在KIRC中的表达和功能作用。我们进行了RT-qPCR分析，以评估FAM3A、FAM3B、FAM3C和FAM3D在KIRC和正常细胞系中的表达，结果显示癌细胞中FAM3A和FAM3D显著上调，FAM3B和FAM3C下调。ROC分析表明，FAM3基因具有较高的诊断潜力。使用TCGA、OncoDB和人类蛋白质图谱（HPA）数据库进行的进一步验证证实了这些表达模式及其与癌症进展的关联。甲基化分析表明，FAM3A和FAM3D低甲基化，FAM3B和FAM3C高甲基化，这与基因表达差异相关。生存分析显示，FAM3A高表达与预后不良相关，而FAM3C低表达与生存率降低相关。功能试验表明，在786-O细胞中敲低FAM3A可降低细胞增殖、克隆形成能力和迁移能力，突出了其在KIRC发病机制中的潜在作用。此外，FAM3基因与免疫细胞浸润、免疫抑制基因和耐药性显著相关，表明它们参与调节肿瘤微环境。miRNA-mRNA网络分析确定hsa-mir-19b-3p是FAM3基因的关键调节因子，进一步表明这些基因与KIRC进展有关。这项综合分析突出了FAM3基因作为KIRC生物标志物和治疗靶点的潜力。
