大量研究表明，转录因子类克鲁佩尔样因子（KLFs）家族调节真核生物的多种生理过程，包括动物细胞的增殖、分化、衰老、死亡和癌变等。此外，它们还参与细胞周期、DNA 修复和免疫反应等关键生物过程的调节。目前的研究重点是研究KLFs在正常生理条件下的作用以及疾病的发生和发展。然而，KLFs 家族基因在透明细胞肾细胞癌 (ccRCC) 中的重要性仍被部分了解；因此，需要深入研究它们在这种癌症中的作用和临床价值。该研究旨在探讨KLF家族基因在ccRCC发生、发展和预后中的作用，并确定相关的潜在生物标志物和治疗靶点。使用R软件分析TCGA数据库中613个ccRCC的RNA测序数据中KLF的表达，并通过UALCAN和GEPIA评估ccRCC中KLF基因的表达。使用来自南昌大学第一附属医院的10对配对ccRCC样本组织和肾癌细胞系进行实时荧光定量PCR分析。使用 R 软件对 TCGA 数据库中 KLF 差异表达的肾透明细胞癌 (KIRC) 样本的总生存期 (OS)、无进展间期 (PFI) 和疾病特异性生存期 (DSS) 进行分析，然后生成列线图预测模型。 GSCALite 评估了 KLF 基因与 miRNA 的相互作用并生成了网络图。使用 STRING 以及 GO 和 KEGG 功能富集分析，分析了与 KLF 突变相关的 50 个邻近基因的蛋白质相互作用网络图。 cBioPortal 确定了 KLF 基因突变的概率及其对 ccRCC 患者 OS 和无病生存 (DFS) 的影响。使用 TIMER 分析 KLF 的免疫细胞浸润。最后，使用 GSCALite 分析 KLF 的药物敏感性和相关作用途径。使用细胞实验进行相关性验证。与癌旁组织相比，KLF3/5/9/15 在 ccRCC 组织中显着下调，而 KLF16/17 上调。 KLF16/17 mRNA 水平较高的患者 OS、PFI 和 DSS 显着降低，而 KLF3/5/9 则呈现相反趋势。在 ccRCC 患者中，观察到 KLF 突变与 OS 和 DSS 之间存在显着相关性。此外，KLF3/5/9与免疫细胞浸润的相关性强于KLF15/16，而KLF17与上皮-间质转化（EMT）途径显着相关。 KLF5的过度表达会抑制肾癌细胞（786-O和OS-RC-2）的增殖和迁移能力，以及它们对相关小分子药物的敏感性。我们的研究揭示了 KLF 基因在 ccRCC 中的表达水平和生物学意义，特别强调了 KLF5 作为 ccRCC 有效预后和诊断的有前途的生物标志物和治疗靶点的潜力。© 2024。作者。

Numerous studies have shown that the Krüppel-like factors (KLFs) family of transcription factors regulate various eukaryotic physiological processes including the proliferation, differentiation, senescence, death, and carcinogenesis of animal cells. In addition, they are involved in the regulation of key biological processes such as cell cycle, DNA repair, and immune response. Current studies focus on investigating the role of KLFs in normal physiological conditions and the incidence and development of diseases. However002C the significance of KLFs family genes in clear cell renal cell carcinoma (ccRCC) remains partly understood; therefore, an in-depth investigation of their role and clinical value in this cancer is desired. The study aimed to investigate the role of KLF family genes in the incidence, development, and prognosis of ccRCC, and to identify the related potential biomarkers and therapeutic targets. The expression of KLFs in the RNA sequencing data of 613 ccRCCs from the TCGA database was analyzed using R software, and UALCAN and GEPIA assessed the expression of KLF genes in ccRCC. Real-time fluorescence quantitative PCR analysis was performed using 10 pairs of paired ccRCC sample tissues and renal cancer cell lines from the First Affiliated Hospital of Nanchang University. Overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) of Kidney Clear Cell Carcinoma (KIRC) samples at differential expressions of KLFs in the TCGA database were analyzed using the R software, followed by generating a nomogram prediction model. GSCALite assessed the interactions of KLF genes with miRNAs and generated network maps. Protein interaction network maps of 50 neighboring genes associated with KLF mutations were analyzed using STRING with GO and KEGG functional enrichment analyses. The cBioPortal determined the probability of KLF gene mutations and their impact on OS and disease-free survival (DFS) in patients with ccRCC. Immune cell infiltration of KLFs was analyzed using TIMER. Finally, GSCALite was used to analyze the drug sensitivity and associated pathways of action of KLFs. Correlation validation using cellular experiments. KLF3/5/9/15 were significantly downregulated in ccRCC tissues, whereas KLF16/17 were upregulated compared with the adjacent tissues. Patients with high mRNA levels of KLF16/17 showed significantly lower OS, PFI, and DSS, whereas KLF3/5/9 showed a reverse trend. In patients with ccRCC, a significant correlation was observed between KLF mutations and OS and DSS. Furthermore, the correlation of KLF3/5/9 with immune cell infiltration was stronger than that of KLF15/16, while KLF17 was significantly associated with the Epithelial-Mesenchymal Transition (EMT) pathway. Overexpression of KLF5 inhibits the proliferative and migratory capacity of renal cancer cells (786-O and OS-RC-2), as well as their sensitivity to relevant small molecule drugs. Our research revealed the expression levels and biological significance of KLF genes in ccRCC, particularly highlighting the potential of KLF5 as a promising biomarker and therapeutic target for effective prognosis and diagnosis of ccRCC.© 2024. The Author(s).