{"title":"In silico research of coagulation- and fibrinolysis-related genes for predicting prognosis of clear cell renal cell carcinoma.","authors":"Ming-Hao Deng, Xue-Wen Yang, Yu-Ming Zhou, Lv-Zhong Xie, Tao Zou, Ji-Gen Ping","doi":"10.21037/tau-24-483","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Sixteen DE-CFRGs were identified by intersecting 3,311 DEGs, 1,719 key module genes, and CFRGs. Four prognostic genes-<i>TIMP1, RUNX1, BMP6</i>, and <i>PROS1</i>-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 <i>TIMP1,</i> and <i>RUNX1</i> were significantly upregulated in ccRCC samples, consistent with bioinformatics analysis.</p><p><strong>Conclusions: </strong>A prognostic model incorporating <i>TIMP1, RUNX1, BMP6</i>, and <i>PROS1</i> was constructed, offering new insights for prognostic evaluation and therapeutic strategies in ccRCC.</p>","PeriodicalId":23270,"journal":{"name":"Translational andrology and urology","volume":"14 2","pages":"307-324"},"PeriodicalIF":1.9000,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921444/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational andrology and urology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tau-24-483","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/25 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ANDROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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-TIMP1, RUNX1, BMP6, and PROS1-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 TIMP1, and RUNX1 were significantly upregulated in ccRCC samples, consistent with bioinformatics analysis.
Conclusions: A prognostic model incorporating TIMP1, RUNX1, BMP6, and PROS1 was constructed, offering new insights for prognostic evaluation and therapeutic strategies in ccRCC.
期刊介绍：
ranslational Andrology and Urology (Print ISSN 2223-4683; Online ISSN 2223-4691; Transl Androl Urol; TAU) is an open access, peer-reviewed, bi-monthly journal (quarterly published from Mar.2012 - Dec. 2014). The main focus of the journal is to describe new findings in the field of translational research of Andrology and Urology, provides current and practical information on basic research and clinical investigations of Andrology and Urology. Specific areas of interest include, but not limited to, molecular study, pathology, biology and technical advances related to andrology and urology. Topics cover range from evaluation, prevention, diagnosis, therapy, prognosis, rehabilitation and future challenges to urology and andrology. Contributions pertinent to urology and andrology are also included from related fields such as public health, basic sciences, education, sociology, and nursing.
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