通过共表达网络鉴定树突状细胞相关基因以构建预测肝细胞癌预后的12基因风险评分模型。

Identifying Dendritic Cell-Related Genes Through a Co-Expression Network to Construct a 12-Gene Risk-Scoring Model for Predicting Hepatocellular Carcinoma Prognosis.

作者信息

Huang Chaoyuan, Jiang Xiaotao, Huang Yuancheng, Zhao Lina, Li Peiwu, Liu Fengbin

机构信息

The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Front Mol Biosci. 2021 May 24;8:636991. doi: 10.3389/fmolb.2021.636991. eCollection 2021.

Abstract

The prognostic prediction of hepatocellular carcinoma (HCC) is still challenging. Immune cells play a crucial role in tumor initiation, progression, and drug resistance. However, prognostic value of immune-related genes in HCC remains to be further clarified. In this study, the mRNA expression profiles and corresponding clinical information of HCC patients were downloaded from public databases. Then, we estimated the abundance of immune cells and identified the differentially infiltrated and prognostic immune cells. The weighted gene co-expression network analysis (WGCNA) was performed to identify immune-related genes in TCGA cohort and GEO cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied to establish a risk-scoring model in the TCGA cohort. HCC patients from the GSE14520 datasets were utilized for risk model validation. Our results found that high level of dendritic cell (DC) infiltration was associated with poor prognosis. Over half of the DC-related genes (58.2%) were robustly differentially expressed between HCC and normal specimens in the TCGA cohort. 17 differentially expressed genes (DEGs) were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. A 12-gene risk-scoring model was established to evaluate the prognosis of HCC. The high-risk group exhibits significantly lower OS rate of HCC patients than the low-risk group. The risk-scoring model shows benign predictive capacity in both GEO dataset and TCGA dataset. The 12-gene risk-scoring model may independently perform prognostic value for HCC patients. Receiver operating characteristic (ROC) curve analysis of the risk-scoring model in GEO cohort and TCGA cohort performed well in predicting OS. Taken together, the 12-gene risk-scoring model could provide prognostic and potentially predictive information for HCC. SDC3, NCF2, BTN3A3, and WARS were noticed as a novel prognostic factor for HCC.

摘要

肝细胞癌(HCC)的预后预测仍然具有挑战性。免疫细胞在肿瘤的发生、发展和耐药性中起着关键作用。然而,免疫相关基因在HCC中的预后价值仍有待进一步阐明。在本研究中,从公共数据库下载了HCC患者的mRNA表达谱和相应的临床信息。然后,我们估计了免疫细胞的丰度,并确定了差异浸润和预后相关的免疫细胞。进行加权基因共表达网络分析(WGCNA)以识别TCGA队列和GEO队列中的免疫相关基因。应用最小绝对收缩和选择算子(LASSO)Cox回归模型在TCGA队列中建立风险评分模型。来自GSE14520数据集的HCC患者用于风险模型验证。我们的结果发现,高水平的树突状细胞(DC)浸润与不良预后相关。在TCGA队列中,超过一半的DC相关基因(58.2%)在HCC和正常标本之间存在显著差异表达。单因素Cox回归分析发现17个差异表达基因(DEG)与总生存期(OS)显著相关。建立了一个12基因风险评分模型来评估HCC的预后。高风险组HCC患者的OS率显著低于低风险组。风险评分模型在GEO数据集和TCGA数据集中均显示出良好的预测能力。12基因风险评分模型可能独立地对HCC患者具有预后价值。对GEO队列和TCGA队列中的风险评分模型进行的受试者工作特征(ROC)曲线分析在预测OS方面表现良好。综上所述,12基因风险评分模型可为HCC提供预后及潜在的预测信息。SDC3、NCF2、BTN3A3和WARS被认为是HCC的新型预后因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d3d/8181399/3fb17b74e50e/fmolb-08-636991-g001.jpg

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