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基于与肿瘤微环境相关基因建立的肝细胞癌患者预后特征。

A prognostic signature established based on genes related to tumor microenvironment for patients with hepatocellular carcinoma.

作者信息

Cui Zhongfeng, Li Ge, Shi Yanbin, Zhao Xiaoli, Wang Juan, Hu Shanlei, Chen Chunguang, Li Guangming

机构信息

Department of Clinical Laboratory, Henan Provincial Infectious Disease Hospital, Zhengzhou 450000, China.

Department of Radiology, Henan Provincial Infectious Disease Hospital, Zhengzhou 450000, China.

出版信息

Aging (Albany NY). 2024 Apr 4;16(7):6537-6549. doi: 10.18632/aging.205722.

Abstract

BACKGROUND

Complex cellular signaling network in the tumor microenvironment (TME) could serve as an indicator for the prognostic classification of hepatocellular carcinoma (HCC) patients.

METHODS

Univariate Cox regression analysis was performed to screen prognosis-related TME-related genes (TRGs), based on which HCC samples were clustered by running non-negative matrix factorization (NMF) algorithm. Furthermore, the correlation between different molecular HCC subtypes and immune cell infiltration level was analyzed. Finally, a risk score (RS) model was established by LASSO and Cox regression analyses (CRA) using these TRGs. Functional enrichment analysis was performed using gene set enrichment analysis (GSEA).

RESULTS

HCC patients were divided into three molecular subtypes (C1, C2, and C3) based on 704 prognosis-related TRGs. HCC subtype C1 had significantly better OS than C2 and C3. We selected 13 TRGs to construct the RS model. Univariate and multivariate CRA showed that the RS could independently predict patients' prognosis. A nomogram integrating the RS and clinicopathologic features of the patients was further created. We also validated the reliability of the model according to the area under the receiver operating characteristic (ROC) curve value, concordance index (C-index), and decision curve analysis. The current findings demonstrated that the RS was significantly correlated with CD8+ T cells, monocytic lineage, and myeloid dendritic cells.

CONCLUSION

This study provided TRGs to help classify patients with HCC and predict their prognoses, contributing to personalized treatments for patients with HCC.

摘要

背景

肿瘤微环境(TME)中复杂的细胞信号网络可作为肝细胞癌(HCC)患者预后分类的指标。

方法

进行单因素Cox回归分析以筛选与预后相关的TME相关基因(TRGs),在此基础上通过运行非负矩阵分解(NMF)算法对HCC样本进行聚类。此外,分析了不同分子HCC亚型与免疫细胞浸润水平之间的相关性。最后,使用这些TRGs通过LASSO和Cox回归分析(CRA)建立风险评分(RS)模型。使用基因集富集分析(GSEA)进行功能富集分析。

结果

基于704个与预后相关的TRGs,HCC患者被分为三种分子亚型(C1、C2和C3)。HCC亚型C1的总生存期明显优于C2和C3。我们选择了13个TRGs来构建RS模型。单因素和多因素CRA显示RS可以独立预测患者的预后。进一步创建了一个整合RS和患者临床病理特征的列线图。我们还根据受试者操作特征(ROC)曲线下面积值、一致性指数(C-index)和决策曲线分析验证了模型的可靠性。目前的研究结果表明,RS与CD8 + T细胞、单核细胞谱系和髓样树突状细胞显著相关。

结论

本研究提供了TRGs以帮助对HCC患者进行分类并预测其预后,有助于为HCC患者提供个性化治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e6c/11042935/8e9d526c9c87/aging-16-205722-g001.jpg

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