RIPK2是肝细胞癌潜在的新型生物标志物和治疗靶点-东南大学学报医学版

RIPK2是肝细胞癌潜在的新型生物标志物和治疗靶点

单位：1. 江苏大学附属武进医院肿瘤科, 江苏常州 213002;
2. 苏州大学附属第三医院肿瘤生物诊疗中心, 江苏常州 213003;
3. 江苏大学附属武进医院消化内科, 江苏常州 213002;
4. 东南大学附属中大医院消化内科, 江苏南京 210009

关键词：肝细胞癌受体相互作用蛋白激酶2 诊断预后生物标志物

分类号：R735.7

出版年·卷·期（页码）：2025·44·第一期（60-66）

摘要：

目的:分析受体相互作用蛋白激酶2(receptor interacting protein kinase 2, RIPK2)在肝细胞癌(hepatocellular carcinoma, HCC)中的表达、临床意义及其与免疫细胞浸润的相关性,探讨其在HCC诊断、预后评估和治疗中的潜在价值。方法:从TCGA数据库收集泛癌及TCGA-LIHC队列中HCC患者的RNA测序和临床数据。分析RIPK2在HCC中的表达及其与临床病理特征的相关性,qRT-PCR验证 RIPK2在HCC中的表达情况。通过Kaplan-Meier生存分析和Cox比例风险回归模型评估RIPK2表达水平对总生存期(overall survival, OS)的影响。采用R包"DESeq2"分析差异表达基因,并进行GO和KEGG富集分析。使用单样本基因集富集分析(ssGSEA)算法评估免疫细胞浸润水平,并探讨其与RIPK2表达的相关性。结果: RIPK2在HCC组织中的表达水平显著高于正常组织,且与组织学分级和血清甲胎蛋白(AFP)水平呈正相关。RIPK2高表达组患者的OS显著低于低表达组。受试者工作特征(ROC)曲线分析显示RIPK2在HCC诊断中具有较高的诊断价值。功能富集分析揭示差异表达基因在免疫反应相关过程中显著富集。RIPK2表达与多种免疫细胞浸润水平相关,尤其是与巨噬细胞、Th2细胞、T细胞和Th1细胞呈正相关,以及与Th17细胞呈负相关。结论: RIPK2在HCC中可能发挥重要作用,并可能成为HCC诊断、预后评估的潜在新型生物标志物和治疗靶点。

Objective: To analyze the expression, clinical significance and correlation with immune cell infiltration of receptor interacting protein kinase 2(RIPK2) in hepatocellular carcinoma(HCC), and to explore its potential value in the diagnosis, prognosis and treatment of HCC. Methods: RNA sequencing and clinical data of HCC patients from the pan-cancer and TCGA-LIHC cohorts were collected from the TCGA database. The expression of RIPK2 in HCC and its correlation with clinicopathological characteristics were analyzed, and the expression of RIPK2 in HCC was verified by qRT-PCR. The effect of RIPK2 expression levels on overall survival(OS) was assessed using Kaplan-Meier survival analysis and Cox proportional hazards regression model. In addition, differentially expressed genes were analyzed using the R package DESeq2 and subjected to GO and KEGG enrichment analysis. The single-sample gene set enrichment analysis(ssGSEA) algorithm was used to assess the level of immune cell infiltration and to explore its correlation with RIPK2 expression. Results: The expression level of RIPK2 in HCC tissue was significantly higher than that in normal tissue and was positively correlated with histological grade and serum alpha-fetoprotein(AFP) levels. Patients in the high RIPK2 expression group had significantly lower OS than those in the low expression group. ROC curve analysis showed that RIPK2 had high diagnostic value in HCC diagnosis. Functional enrichment analysis revealed that differentially expressed genes were significantly enriched in immune response-related processes. The expression of RIPK2 was correlated with the infiltration levels of various immune cells, particularly having a positive correlation with macrophages, Th2 cells, T cells, and Th1 cells, and a negative correlation with Th17 cells. Conclusion: RIPK2 may play an important role in HCC and may become a potential novel biomarker for HCC diagnosis and prognosis, as well as a therapeutic target.

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