Golestanifar Ahmad, Khedri Hengameh, Noorabadi Parisa, Saberiyan Mohammadreza
Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Department of Internal Medicine, School of Medicine, Urmia University of Medical sciences, Urmia, Iran.
Biochem Biophys Rep. 2025 Feb 1;41:101942. doi: 10.1016/j.bbrep.2025.101942. eCollection 2025 Mar.
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults. RCC begins in the renal tubule epithelial cells, essential for blood filtration and urine production.
In this study, we aim to uncover the molecular mechanisms underlying kidney renal clear cell carcinoma (KIRC) by analyzing various non-coding RNAs (ncRNAs) and protein-coding genes involved in the disease. Using high-throughput sequencing datasets from the Gene Expression Omnibus (GEO), we identified differentially expressed mRNAs (DEMs), miRNAs (DEMIs), and circRNAs (DECs) in KIRC samples compared to normal kidney tissues. Our approach combined differential expression analysis, functional enrichment through Gene Ontology (GO) and KEGG pathway mapping, and a Protein-Protein Interaction (PPI) network to identify crucial hub genes in KIRC progression.
Key findings include the identification of hub genes such as EGFR, FN1, IL6, and ITGAM, which were closely associated with immune responses, cell signaling, and metabolic dysregulation in KIRC. Further analysis indicated that these genes could be potential biomarkers for prognosis and therapeutic targets. We constructed a competitive endogenous RNA (ceRNA) network involving lncRNAs, circRNAs, and miRNAs, suggesting complex regulatory interactions that drive KIRC pathogenesis.Additionally, the study examined drug sensitivity associated with the expression of hub genes, revealing the potential for personalized treatments. Immune cell infiltration patterns showed significant correlations with hub gene expression, highlighting the importance of immune modulation in KIRC.
This research provides a foundation for developing targeted therapies and diagnostic biomarkers for KIRC while underscoring the need for experimental validation to confirm these bioinformatics insights.
肾细胞癌（RCC）是成人中最常见的肾癌类型。RCC起源于肾小管上皮细胞，这些细胞对血液过滤和尿液生成至关重要。
在本研究中，我们旨在通过分析参与该疾病的各种非编码RNA（ncRNAs）和蛋白质编码基因，揭示肾透明细胞癌（KIRC）潜在的分子机制。利用来自基因表达综合数据库（GEO）的高通量测序数据集，我们鉴定了与正常肾组织相比，KIRC样本中差异表达的mRNA（DEMs）、miRNA（DEMIs）和环状RNA（DECs）。我们的方法结合了差异表达分析、通过基因本体论（GO）和KEGG通路映射进行的功能富集，以及蛋白质-蛋白质相互作用（PPI）网络，以识别KIRC进展中的关键枢纽基因。
主要发现包括鉴定出如EGFR、FN1、IL6和ITGAM等枢纽基因，这些基因与KIRC中的免疫反应、细胞信号传导和代谢失调密切相关。进一步分析表明，这些基因可能是预后的潜在生物标志物和治疗靶点。我们构建了一个涉及lncRNA、circRNA和miRNA的竞争性内源RNA（ceRNA）网络，表明驱动KIRC发病机制的复杂调控相互作用。此外，该研究检查了与枢纽基因表达相关的药物敏感性，揭示了个性化治疗的潜力。免疫细胞浸润模式与枢纽基因表达显示出显著相关性，突出了免疫调节在KIRC中的重要性。
本研究为开发KIRC的靶向治疗和诊断生物标志物提供了基础，同时强调需要进行实验验证以证实这些生物信息学见解。
