PDF(Pubmed)
Abstract：
UNASSIGNED: Numerous studies have revealed a tight connection between tumor development and the coagulation system. However, the effects of coagulation on the prognosis and tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) remain poorly understood.
UNASSIGNED: We employed the consensus clustering method to characterize distinct molecular subtypes associated with coagulation patterns. Subsequently, we examined variations in the overall survival (OS), genomic profiles, and TME characteristics between these subtypes. To develop a prognostic coagulation-related risk score (CRRS) model, we utilized the least absolute shrinkage and selection operator Cox regression and stepwise multivariate Cox regression analyses. We also created a nomogram to aid in the clinical application of the risk score, evaluating the relationships between the CRRS and the immune microenvironment, responsiveness to immunotherapy, and targeted treatment. The clinical significance of PLAUR and its biological function in ccRCC were also further analyzed.
UNASSIGNED: There were significant differences in clinical features, prognostic stratification, genomic variation, and TME characteristics between the two coagulation-related subtypes. We established and validated a CRRS using six coagulation-related genes that can be employed as an effective indicator of risk stratification and prognosis estimation for ccRCC patients. Significant variations in survival outcomes were observed between the high- and low-risk groups. The nomogram was proficient in predicting the 1-, 3-, and 5-year OS. Additionally, the CRRS emerged as a novel tool for evaluating the clinical effectiveness of immunotherapy and targeted treatments in ccRCC. Moreover, we confirmed upregulated PLAUR expression in ccRCC samples that was significantly correlated with poor patient prognosis. PLAUR knockdown notably inhibited ccRCC cell proliferation and migration.
UNASSIGNED: Our data suggested that CRRS may be employed as a reliable predictive biomarker that can provide therapeutic benefits for immunotherapy and targeted therapy in ccRCC.
UNASSIGNED: We employed the consensus clustering method to characterize distinct molecular subtypes associated with coagulation patterns. Subsequently, we examined variations in the overall survival (OS), genomic profiles, and TME characteristics between these subtypes. To develop a prognostic coagulation-related risk score (CRRS) model, we utilized the least absolute shrinkage and selection operator Cox regression and stepwise multivariate Cox regression analyses. We also created a nomogram to aid in the clinical application of the risk score, evaluating the relationships between the CRRS and the immune microenvironment, responsiveness to immunotherapy, and targeted treatment. The clinical significance of PLAUR and its biological function in ccRCC were also further analyzed.
UNASSIGNED: There were significant differences in clinical features, prognostic stratification, genomic variation, and TME characteristics between the two coagulation-related subtypes. We established and validated a CRRS using six coagulation-related genes that can be employed as an effective indicator of risk stratification and prognosis estimation for ccRCC patients. Significant variations in survival outcomes were observed between the high- and low-risk groups. The nomogram was proficient in predicting the 1-, 3-, and 5-year OS. Additionally, the CRRS emerged as a novel tool for evaluating the clinical effectiveness of immunotherapy and targeted treatments in ccRCC. Moreover, we confirmed upregulated PLAUR expression in ccRCC samples that was significantly correlated with poor patient prognosis. PLAUR knockdown notably inhibited ccRCC cell proliferation and migration.
UNASSIGNED: Our data suggested that CRRS may be employed as a reliable predictive biomarker that can provide therapeutic benefits for immunotherapy and targeted therapy in ccRCC.
摘要：
■许多研究表明，肿瘤的发展与凝血系统之间存在紧密的联系。然而,凝血功能对肾透明细胞癌(ccRCC)预后和肿瘤微环境(TME)的影响尚不清楚。
■我们采用共识聚类方法来表征与凝血模式相关的不同分子亚型。随后，我们检查了总生存期(OS)的变化，基因组概况，和这些亚型之间的TME特征。建立预后凝血相关风险评分(CRRS)模型,我们利用最小绝对收缩率和选择算子Cox回归和逐步多变量Cox回归分析.我们还创建了一个列线图来帮助风险评分的临床应用，评估CRRS与免疫微环境之间的关系，对免疫疗法的反应，有针对性的治疗。进一步分析PLAUR的临床意义及其在ccRCC中的生物学功能。
■临床特征有显著差异，预后分层，基因组变异，两种凝血相关亚型之间的TME特征。我们使用六个凝血相关基因建立并验证了CRRS，这些基因可以用作ccRCC患者风险分层和预后评估的有效指标。在高危组和低危组之间观察到生存结果的显着差异。列线图精通预测1-，3-,5年OS此外,CRRS成为评估ccRCC免疫治疗和靶向治疗临床有效性的新工具.此外，我们证实ccRCC样本中PLAUR表达上调,这与患者预后不良显著相关.PLAUR敲除显著抑制ccRCC细胞增殖和迁移。
■我们的数据表明CRRS可以用作可靠的预测性生物标志物，可以为ccRCC的免疫治疗和靶向治疗提供治疗益处。
■我们采用共识聚类方法来表征与凝血模式相关的不同分子亚型。随后，我们检查了总生存期(OS)的变化，基因组概况，和这些亚型之间的TME特征。建立预后凝血相关风险评分(CRRS)模型,我们利用最小绝对收缩率和选择算子Cox回归和逐步多变量Cox回归分析.我们还创建了一个列线图来帮助风险评分的临床应用，评估CRRS与免疫微环境之间的关系，对免疫疗法的反应，有针对性的治疗。进一步分析PLAUR的临床意义及其在ccRCC中的生物学功能。
■临床特征有显著差异，预后分层，基因组变异，两种凝血相关亚型之间的TME特征。我们使用六个凝血相关基因建立并验证了CRRS，这些基因可以用作ccRCC患者风险分层和预后评估的有效指标。在高危组和低危组之间观察到生存结果的显着差异。列线图精通预测1-，3-,5年OS此外,CRRS成为评估ccRCC免疫治疗和靶向治疗临床有效性的新工具.此外，我们证实ccRCC样本中PLAUR表达上调,这与患者预后不良显著相关.PLAUR敲除显著抑制ccRCC细胞增殖和迁移。
■我们的数据表明CRRS可以用作可靠的预测性生物标志物，可以为ccRCC的免疫治疗和靶向治疗提供治疗益处。
