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免疫相关基因在预测肝癌患者预后和免疫反应中的作用。

Role of immune related genes in predicting prognosis and immune response in patients with hepatocellular carcinoma.

机构信息

Departments of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People's Republic of China.

出版信息

J Biochem Mol Toxicol. 2024 Jan;38(1):e23519. doi: 10.1002/jbt.23519. Epub 2023 Sep 4.

Abstract

Immunotherapy has developed rapidly in recent years. This study aimed to establish a prognostic signature for immune-related genes (IRGs) and explore related potential immunotherapies. The RNA-seq transcriptome profiles and clinicopathological information of patients were obtained from The Cancer Genome Atlas. Differentially expressed IRGs in tumors and normal tissues were screened and a risk score signature was constructed to predict the prognosis in patients with hepatocellular carcinoma (HCC). Receiver operating characteristic curves, survival analyses, and correlation analyses were used to explore the clinical application of this model. We further analyzed the differences in clinical characteristics, immune infiltration, somatic mutations, and treatment sensitivity between the high- and low-risk populations characterized by the prognostic models. The immune cell infiltration score and immune-related pathway activity were calculated using the single sample gene set enrichment analysis (ssGSEA) set enrichment analysis. Gene ontology (GO), Kyoto encyclopedia of genes and genomes, and GSEA were used to explore the underlying mechanisms. We constructed a nine-IRG formula to predict the prognosis in HCC patients. The higher the risk score, the higher the malignancy of the tumor and the worse the prognosis. There were significant differences in immune related processes between the high- and low-risk groups. TP53 and CTNNB1 mutations were significantly different between different risk groups. The expression of model gene was closely related to the sensitivity of tumor cells to chemotherapeutic drugs. This risk score model, which is helpful for the individualized treatment of patients with different risk factors, could be a reliable prognostic tool for HCC patients.

摘要

免疫疗法近年来发展迅速。本研究旨在建立免疫相关基因(IRGs)的预后特征,并探讨相关的潜在免疫疗法。从癌症基因组图谱中获取了患者的 RNA-seq 转录组谱和临床病理信息。筛选肿瘤和正常组织中差异表达的 IRGs,并构建风险评分特征以预测肝细胞癌(HCC)患者的预后。使用受试者工作特征曲线、生存分析和相关性分析来探讨该模型的临床应用。我们进一步分析了由预后模型特征化的高风险和低风险人群的临床特征、免疫浸润、体细胞突变和治疗敏感性的差异。使用单样本基因集富集分析(ssGSEA)对免疫细胞浸润评分和免疫相关途径活性进行了计算。使用基因本体论(GO)、京都基因与基因组百科全书和 GSEA 对潜在机制进行了探讨。我们构建了一个九基因公式来预测 HCC 患者的预后。风险评分越高,肿瘤的恶性程度越高,预后越差。高风险组和低风险组之间的免疫相关过程存在显著差异。不同风险组之间的 TP53 和 CTNNB1 突变存在显著差异。模型基因的表达与肿瘤细胞对化疗药物的敏感性密切相关。该风险评分模型有助于针对不同风险因素的患者进行个体化治疗,可能成为 HCC 患者可靠的预后工具。

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