补体和凝血级联相关基因的新型预后模型与肝细胞癌的免疫环境及药物敏感性相关。
Novel prognostic model of complement and coagulation cascade-related genes correlates with immune environment and drug sensitivity in hepatocellular carcinoma.
作者信息
Su Hui, Chen Yunjie, Wang Wuke
机构信息
Department of General Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China.
Ningbo Institute of Life and Health Industry, Ningbo No.2 Hospital, Ningbo, Zhejiang, China.
出版信息
Heliyon. 2024 Sep 20;10(19):e38230. doi: 10.1016/j.heliyon.2024.e38230. eCollection 2024 Oct 15.
INTRODUCTION
Hepatocellular carcinoma (HCC) is an immunogenic cancer characterized by high morbidity and mortality rates. The complement and coagulation systems are traditionally associated with the incidence of thrombotic complications and complement activation in cancer. However, the prognostic value of complement and coagulation-related factors (CCCR) in HCC remains undetermined. This study aims to construct a prognostic model based on the complement and coagulation cascades to evaluate its potential for immunotherapy and its relationship with drug sensitivity.
MATERIALS AND METHODS
We comprehensively investigated the expression profiles of CCCR genes using the TCGA, ICGC, and GTEx databases. Cox proportional hazards regression models were employed to assess prognostic value.
RESULTS
This study presents a novel prognostic model derived from the comprehensive analysis of nine CCCR genes (C1S, C6, C7, F11, F13B, F7, SERPINE1, SERPINF2, and SERPING1) to elucidate their correlation with the tumor immune environment and drug sensitivity in patients with HCC. Our model stratified patients into high- and low-risk groups based on distinct survival outcomes. The area under the curve (AUC) values of the risk score for one-, two-, and three-year survival rates were all greater than 0.660. Additionally, we analyzed immune cell infiltration patterns, revealing a strong correlation between CCCR gene expression and the immune microenvironment, including T cell and macrophage activity. Our findings also identified potential therapeutic targets, demonstrating differential drug sensitivity profiles between the risk groups. JAK1_8709_1718 was found to be more suitable for patients with low-risk HCC.
CONCLUSION
Our findings provide promising insights into the clinical relevance of CCCR genes as prognostic markers and therapeutic targets. This study underscores the significance of CCCR in HCC and paves the way for improved therapeutic strategies.
引言
肝细胞癌(HCC)是一种具有免疫原性的癌症,发病率和死亡率都很高。传统上,补体和凝血系统与癌症中血栓并发症的发生及补体激活有关。然而,补体和凝血相关因子(CCCR)在HCC中的预后价值仍未确定。本研究旨在构建一个基于补体和凝血级联反应的预后模型,以评估其在免疫治疗中的潜力及其与药物敏感性的关系。
材料与方法
我们使用TCGA、ICGC和GTEx数据库全面研究了CCCR基因的表达谱。采用Cox比例风险回归模型评估预后价值。
结果
本研究通过对9个CCCR基因(C1S、C6、C7、F11、F13B、F7、SERPINE1、SERPINF2和SERPING1)的综合分析,提出了一种新的预后模型,以阐明它们与HCC患者肿瘤免疫环境和药物敏感性的相关性。我们的模型根据不同的生存结果将患者分为高风险和低风险组。一年、两年和三年生存率的风险评分曲线下面积(AUC)值均大于0.660。此外,我们分析了免疫细胞浸润模式,发现CCCR基因表达与免疫微环境之间存在密切相关性,包括T细胞和巨噬细胞活性。我们的研究结果还确定了潜在的治疗靶点,显示了风险组之间不同的药物敏感性谱。发现JAK1_8709_1718更适合低风险HCC患者。
结论
我们的研究结果为CCCR基因作为预后标志物和治疗靶点的临床相关性提供了有前景的见解。本研究强调了CCCR在HCC中的重要性,并为改进治疗策略铺平了道路。
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