Clear cell renal cell carcinoma (ccRCC) is a highly aggressive disease and ∼30% of the patients are diagnosed at the metastatic stage. Even with new targeted therapies, the average progression-free survival and overall survival (OS) rates are dismal. Thus, biomarkers for early detection and progression could improve disease outcome. The role of C1q/tumor necrosis factor (C1QTNF) family in cancer is an emerging field of research. However, the biological function of C1q/tumor necrosis factor-related protein 6 (C1QTNF6) and its prognostic value in cancer are rarely reported. This study aimed to evaluate C1QTNF6 as a potential diagnostic and prognostic biomarker for ccRCC. In this study, we enrolled 993 ccRCC samples (data from our cohort, The Cancer Genome Atlas, and Gene Expression Omnibus) with C1QTNF6 expression to explore its role and mechanism in ccRCC. The diagnostic power of C1QTNF6 was determined by receiver operating characteristic curve analysis and its prognostic value was evaluated by Kaplan–Meier analysis and Cox regression models, respectively. In addition, the gene set enrichment analysis was performed to unveil the molecular mechanism of C1QTNF6 in ccRCC. We demonstrated that C1QTNF6 was overexpressed in ccRCC, and elevated C1QTNF6 expression correlated with clinical progression. Besides, C1QTNF6 served as a new diagnostic biomarker for renal cell carcinoma. Moreover, C1QTNF6 is an independent risk factor for OS in ccRCC patients. Furthermore, C1QTNF6-related signaling pathways activated in ccRCC are mainly enriched in cell cycle, epithelial–mesenchymal transition, and angiogenesis signaling pathways. Taken together, our results provided insights in understanding the potential role of C1QTNF6 in promoting tumor growth, invasion, and metastasis, and its use as a novel cancer diagnostic and prognostic biomarker for ccRCC.

中文翻译：

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C1QTNF6作为透明细胞肾细胞癌的新型诊断和预后生物标志物。

透明细胞肾细胞癌（ccRCC）是一种高度侵袭性疾病，约30％的患者被诊断为转移期。即使采用了新的靶向疗法，平均无进展生存期和总生存期（OS）的比率也是令人沮丧的。因此，用于早期发现和进展的生物标志物可以改善疾病的预后。C1q /肿瘤坏死因子（C1QTNF）家族在癌症中的作用是一个新兴的研究领域。然而，很少报道C1q /肿瘤坏死因子相关蛋白6（C1QTNF6）的生物学功能及其在癌症中的预后价值。这项研究旨在评估C1QTNF6作为ccRCC的潜在诊断和预后生物标志物。在这项研究中，我们收集了993个ccRCC样本（来自我们的队列，《癌症基因组图谱》和《基因表达综合》的数据），并使用C1QTNF6进行表达，以探讨其在ccRCC中的作用和机制。C1QTNF6的诊断能力通过接受者操作特征曲线分析确定，其预后价值分别通过Kaplan-Meier分析和Cox回归模型评估。此外，进行了基因集富集分析以揭示ccRCC中C1QTNF6的分子机制。我们证明了C1QTNF6在ccRCC中过表达，并且升高的C1QTNF6表达与临床进展相关。除了，C1QTNF6作为肾细胞癌的新诊断生物标志物。此外，C1QTNF6是ccRCC患者OS的独立危险因素。此外，在ccRCC中激活的与C1QTNF6相关的信号传导途径主要丰富于细胞周期，上皮-间充质转化和血管生成信号传导途径。综上所述，我们的结果为了解C1QTNF6在促进肿瘤生长，侵袭和转移中的潜在作用以及将其用作ccRCC的新型癌症诊断和预后生物标志物提供了见识。