Department of Pharmacy, Gaochun People's Hospital, Gaochun Hospital Affiliated to Jiangsu University, Nanjing, 211300, China.
Department of Hospital Infection Management Section, Gaochun People's Hospital, Gaochun Hospital Affiliated to Jiangsu University, Nanjing, 211300, China.
Diagn Pathol. 2024 Aug 2;19(1):105. doi: 10.1186/s13000-024-01528-8.
Hepatocellular carcinoma (HCC) is a malignant tumor. It is estimated that approximately 50-80% of HCC cases worldwide are caused by hepatitis b virus (HBV) infection, and other pathogenic factors have been shown to promote the development of HCC when coexisting with HBV. Understanding the molecular mechanisms of HBV-induced hepatocellular carcinoma (HBV-HCC) is crucial for the prevention, diagnosis, and treatment of the disease. In this study, we analyzed the molecular mechanisms of HBV-induced HCC by combining bioinformatics and deep learning methods. Firstly, we collected a gene set related to HBV-HCC from the GEO database, performed differential analysis and WGCNA analysis to identify genes with abnormal expression in tumors and high relevance to tumors. We used three deep learning methods, Lasso, random forest, and SVM, to identify key genes RACGAP1, ECT2, and NDC80. By establishing a diagnostic model, we determined the accuracy of key genes in diagnosing HBV-HCC. In the training set, RACGAP1(AUC:0.976), ECT2(AUC:0.969), and NDC80 (AUC: 0.976) showed high accuracy. They also exhibited good accuracy in the validation set: RACGAP1(AUC:0.878), ECT2(AUC:0.731), and NDC80(AUC:0.915). The key genes were found to be highly expressed in liver cancer tissues compared to normal liver tissues, and survival analysis indicated that high expression of key genes was associated with poor prognosis in liver cancer patients. This suggests a close relationship between key genes RACGAP1, ECT2, and NDC80 and the occurrence and progression of HBV-HCC. Molecular docking results showed that the key genes could spontaneously bind to the anti-hepatocellular carcinoma drugs Lenvatinib, Regorafenib, and Sorafenib with strong binding activity. Therefore, ECT2, NDC80, and RACGAP1 may serve as potential biomarkers for the diagnosis of HBV-HCC and as targets for the development of targeted therapeutic drugs.
肝细胞癌(HCC)是一种恶性肿瘤。据估计,全球约有 50-80%的 HCC 病例是由乙型肝炎病毒(HBV)感染引起的,其他致病因素已被证明在与 HBV 共存时会促进 HCC 的发展。了解 HBV 诱导的肝细胞癌(HBV-HCC)的分子机制对于疾病的预防、诊断和治疗至关重要。在这项研究中,我们结合生物信息学和深度学习方法分析了 HBV 诱导 HCC 的分子机制。首先,我们从 GEO 数据库中收集了一个与 HBV-HCC 相关的基因集,通过差异分析和 WGCNA 分析,鉴定出肿瘤中表达异常且与肿瘤高度相关的基因。我们使用三种深度学习方法,Lasso、随机森林和 SVM,来识别关键基因 RACGAP1、ECT2 和 NDC80。通过建立诊断模型,我们确定了关键基因诊断 HBV-HCC 的准确性。在训练集中,RACGAP1(AUC:0.976)、ECT2(AUC:0.969)和 NDC80(AUC:0.976)表现出较高的准确性。它们在验证集中也表现出了较好的准确性:RACGAP1(AUC:0.878)、ECT2(AUC:0.731)和 NDC80(AUC:0.915)。与正常肝组织相比,关键基因在肝癌组织中表达较高,生存分析表明,关键基因的高表达与肝癌患者的预后不良相关。这表明关键基因 RACGAP1、ECT2 和 NDC80 与 HBV-HCC 的发生和发展密切相关。分子对接结果表明,关键基因可以与抗肝癌药物仑伐替尼、瑞戈非尼和索拉非尼自发结合,具有很强的结合活性。因此,ECT2、NDC80 和 RACGAP1 可能作为 HBV-HCC 诊断的潜在生物标志物和靶向治疗药物开发的靶点。