Clinical significance, molecular characterization, and immune microenvironment analysis of coagulation-related genes in clear cell renal cell carcinoma

Cancer Innovation Pub Date : 2024-01-07 DOI:10.1002/cai2.105
Weihao Chen, Xupeng Zhao, Yongliang Lu, Hanfeng Wang, Xiyou Wang, Yi Wang, Chen Liang, Zhuomin Jia, Wei Ma
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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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透明细胞肾细胞癌中凝血相关基因的临床意义、分子特征和免疫微环境分析
大量研究揭示了肿瘤发生与凝血系统之间的紧密联系。然而,人们对凝血对透明细胞肾细胞癌(ccRCC)的预后和肿瘤微环境(TME)的影响仍然知之甚少。随后,我们研究了这些亚型之间在总生存期(OS)、基因组图谱和TME特征方面的差异。为了建立预后凝血相关风险评分(CRRS)模型,我们采用了最小绝对缩减和选择操作者 Cox 回归和逐步多变量 Cox 回归分析。我们还创建了一个提名图来帮助风险评分的临床应用,评估 CRRS 与免疫微环境、免疫疗法反应性和靶向治疗之间的关系。两种凝血相关亚型的临床特征、预后分层、基因组变异和TME特征均存在显著差异。我们利用六个凝血相关基因建立并验证了CRRS,它可作为ccRCC患者风险分层和预后评估的有效指标。高危组和低危组之间的生存结果存在显著差异。提名图能很好地预测1年、3年和5年的OS。此外,CRRS还是评估免疫疗法和靶向治疗对ccRCC临床疗效的一种新工具。此外,我们还证实了 PLAUR 在 ccRCC 样本中的表达上调与患者的不良预后显著相关。我们的数据表明,CRRS可作为一种可靠的预测性生物标记物,为ccRCC的免疫疗法和靶向疗法提供疗效。
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