Department of Hepatobiliary Pancreatic Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China.
Clin Invest Med. 2021 Oct 3;44(3):E32-44. doi: 10.25011/cim.v44i3.37124.
Purpose: This study aimed to screen hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC)-related feature ribonucleic acids (RNAs) and to establish a prognostic model. Methods: The transcriptome expression data of HBV-associated HCC were downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus database. Differential RNAs between HBV-associated HCC and normal controls were identified by a meta-analysis of TCGA, GSE55092 and GSE121248. Weighted gene co-expression network analysis was performed to identify key RNAs and modules. A prognostic score model was established using TCGA as a training set by Cox regression analysis and was validated in E-TABM-36 dataset. Additionally, independent prognostic clinical factors were screened, and the function of lncRNAs was predicted through Gene Set Enrichment Analysis. Results: A total of 710 consistent differential RNAs between HBV-associated HCC and normal controls were obtained, including five lncRNAs and 705 mRNAs. An optimized combination of six differential RNAs (DSCR4, DBH, ECM1, GDAP1, MATR3 and RFC4) was selected and a prognostic score model was constructed. Kaplan-Meier analysis demonstrated that the prognosis of the high-risk and low-risk groups separated by this model was significantly different in the training set and the validation set. Gene Set Enrichment Analysis showed that the co-expression genes of DSCR4 were significantly correlated with neuroactive ligand receptor interaction pathway. Conclusion: A prognostic model based on DSCR4, DBH, ECM1, GDAP1, MATR3 and RFC4 was developed that can accurately predict the prognosis of patients with HBV-associated HCC. These genes, as well as histologic grade, may serve as independent prognostic factors in HBV-associated HCC.
本研究旨在筛选乙型肝炎病毒(HBV)相关肝细胞癌(HCC)相关特征的核糖核酸(RNAs),并建立一个预后模型。
从癌症基因组图谱(TCGA)数据库和基因表达综合数据库下载 HBV 相关 HCC 的转录组表达数据。通过 TCGA、GSE55092 和 GSE121248 的荟萃分析,鉴定 HBV 相关 HCC 与正常对照之间的差异 RNA。采用加权基因共表达网络分析鉴定关键 RNA 和模块。通过 Cox 回归分析,使用 TCGA 作为训练集建立预后评分模型,并在 E-TABM-36 数据集进行验证。此外,筛选独立的预后临床因素,并通过基因集富集分析预测 lncRNA 的功能。
获得了 710 个 HBV 相关 HCC 与正常对照之间的一致性差异 RNA,包括 5 个 lncRNA 和 705 个 mRNA。选择了 6 个差异 RNA(DSCR4、DBH、ECM1、GDAP1、MATR3 和 RFC4)的最佳组合,并构建了预后评分模型。Kaplan-Meier 分析表明,该模型在训练集和验证集中,高风险和低风险组的预后差异有统计学意义。基因集富集分析显示,DSCR4 的共表达基因与神经活性配体受体相互作用途径显著相关。
建立了一个基于 DSCR4、DBH、ECM1、GDAP1、MATR3 和 RFC4 的预后模型,可以准确预测 HBV 相关 HCC 患者的预后。这些基因以及组织学分级可能是 HBV 相关 HCC 的独立预后因素。