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一种预测肝细胞癌预后和免疫治疗反应的免疫相关基因特征。

An Immune-Related Gene Signature Predicting Prognosis and Immunotherapy Response in Hepatocellular Carcinoma.

机构信息

Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China.

Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha 410078, China.

出版信息

Comb Chem High Throughput Screen. 2022;25(13):2203-2216. doi: 10.2174/1386207325666220304115006.

DOI:10.2174/1386207325666220304115006
PMID:35249477
Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is inflammation-associated cancer with high incidence and poor prognosis. In the last decade, immunotherapy has become an important strategy for managing HCC.

OBJECTIVE

This study aimed to establish an immune-related gene signature for predicting prognosis and immunotherapy response in HCC.

METHODS

We identified immune-related differentially expressed genes (IRDEGs) based on The Cancer Genome Atlas (TCGA) database and the Immunology Database and Analysis Portal (ImmPort) database. The weighted gene co-expression network analysis (WGCNA) and Cox proportional hazard model were utilized to determine hub immune-related genes (IRGs). The TIDE tool and R package pRRophetic were used to assess the correlation between the immune-related gene signature and the clinical responses to immunotherapy and chemotherapy.

RESULTS

By using WGCNA combined with Cox proportional hazard model, PRC1, TOP2A, TPX2, and ANLN were identified as hub IRGs. The prognostic value of the newly developed gene signature (IRGPI) was demonstrated in both the TCGA database and the Gene Expression Omnibus (GEO) database. The TIDE tool showed that the high- and low-IRGPI groups presented significantly different tumor immune microenvironment and immunotherapy responses. Furthermore, the high-IRGPI group also had significantly lower chemoresistance to cisplatin than the low-IRGPI group.

CONCLUSION

The IRGPI is a tool for predicting prognosis as well as responsiveness to immunotherapy and chemotherapy in HCC.

摘要

背景

肝细胞癌(HCC)是一种炎症相关的癌症,具有高发病率和预后不良的特点。在过去的十年中,免疫疗法已成为治疗 HCC 的重要策略。

目的

本研究旨在建立一个免疫相关基因特征,用于预测 HCC 的预后和免疫治疗反应。

方法

我们基于癌症基因组图谱(TCGA)数据库和免疫数据库和分析门户(ImmPort)数据库,确定了免疫相关差异表达基因(IRDEGs)。利用加权基因共表达网络分析(WGCNA)和 Cox 比例风险模型确定关键免疫相关基因(IRGs)。使用 TIDE 工具和 R 包 pRRophetic 评估免疫相关基因特征与免疫治疗和化疗临床反应之间的相关性。

结果

通过使用 WGCNA 结合 Cox 比例风险模型,确定了 PRC1、TOP2A、TPX2 和 ANLN 为关键 IRGs。新开发的基因特征(IRGPI)在 TCGA 数据库和基因表达综合(GEO)数据库中的预后价值均得到了验证。TIDE 工具表明,高和低 IRGPI 组的肿瘤免疫微环境和免疫治疗反应存在显著差异。此外,高 IRGPI 组对顺铂的化疗耐药性也显著低于低 IRGPI 组。

结论

IRGPI 是一种预测 HCC 预后以及对免疫治疗和化疗反应的工具。

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