用于预测透明细胞肾细胞癌预后的凝血和纤溶相关基因的计算机研究
In silico research of coagulation- and fibrinolysis-related genes for predicting prognosis of clear cell renal cell carcinoma.
作者信息
Deng Ming-Hao, Yang Xue-Wen, Zhou Yu-Ming, Xie Lv-Zhong, Zou Tao, Ping Ji-Gen
机构信息
Department of Urology, Nantong Hospital of Traditional Chinese Medicine, Nantong, China.
Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, China.
出版信息
Transl Androl Urol. 2025 Feb 28;14(2):307-324. doi: 10.21037/tau-24-483. Epub 2025 Feb 25.
BACKGROUND
Coagulation- and fibrinolysis-related genes (CFRGs) are involved in tumor progression. However, their regulatory mechanisms in clear cell renal cell carcinoma (ccRCC) remain unclear. The aim of this study was to search for genes related to coagulation and fibrinolytic systems in ccRCC and to investigate their potential role in tumor pathogenesis and progression.
METHODS
Differentially expressed genes (DEGs) between ccRCC and control samples, as well as key module genes associated with ccRCC, were extracted from The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) dataset. Differentially expressed CFRGs (DE-CFRGs) were identified by intersecting these DEGs with CFRGs. Prognostic genes were identified through univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analyses of DE-CFRGs. Additional independent prognostic and enrichment analyses were conducted, and potential therapeutic drugs were predicted. In addition, quantitative real-time polymerase chain reaction (RT-qPCR) was performed to validate the expression of prognostic genes.
RESULTS
Sixteen DE-CFRGs were identified by intersecting 3,311 DEGs, 1,719 key module genes, and CFRGs. Four prognostic genes-, and -were found to be involved in complement and coagulation cascades and other functional pathways. The prognostic model demonstrated strong predictive power for ccRCC, with stage, risk score, and grade all correlating with prognosis. Additionally, 14 potential drugs, such as tamoxifen citrate and cytarabine, were predicted for therapeutic targeting of the identified prognostic genes. RT-qPCR confirmed that the expression levels of and were significantly upregulated in ccRCC samples, consistent with bioinformatics analysis.
CONCLUSIONS
A prognostic model incorporating , and was constructed, offering new insights for prognostic evaluation and therapeutic strategies in ccRCC.
背景
凝血和纤维蛋白溶解相关基因（CFRGs）参与肿瘤进展。然而，它们在肾透明细胞癌（ccRCC）中的调控机制仍不清楚。本研究的目的是寻找ccRCC中与凝血和纤维蛋白溶解系统相关的基因，并研究它们在肿瘤发病机制和进展中的潜在作用。
方法
从癌症基因组图谱-肾透明细胞癌（TCGA-KIRC）数据集中提取ccRCC与对照样本之间的差异表达基因（DEGs）以及与ccRCC相关的关键模块基因。通过将这些DEGs与CFRGs相交来鉴定差异表达的CFRGs（DE-CFRGs）。通过对DE-CFRGs进行单变量Cox、最小绝对收缩和选择算子（LASSO）以及多变量Cox分析来鉴定预后基因。进行了额外的独立预后和富集分析，并预测了潜在的治疗药物。此外，进行了定量实时聚合酶链反应（RT-qPCR）以验证预后基因的表达。
结果
通过将3311个DEGs、1719个关键模块基因和CFRGs相交，鉴定出16个DE-CFRGs。发现4个预后基因参与补体和凝血级联反应以及其他功能途径。该预后模型对ccRCC具有很强的预测能力，分期、风险评分和分级均与预后相关。此外，预测了14种潜在药物，如柠檬酸他莫昔芬和阿糖胞苷，用于靶向治疗已鉴定的预后基因。RT-qPCR证实，在ccRCC样本中，和的表达水平显著上调，与生物信息学分析一致。
结论
构建了一个包含、和的预后模型，为ccRCC的预后评估和治疗策略提供了新的见解。
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