Liu Baiyi, Wang Xiaoxiao, Wu Nan, Liu Feng, Rao Huiying
Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China.
Peking University People\'s Hospital Peking University Hepatology Institute Beijing China.
Curr Med Chem. 2024 Feb 21. doi: 10.2174/0109298673288887240212065116.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. With an increasing number of patients, NAFLD has been identified as a risk factor for Hepatocellular Carcinoma (HCC). The precise pathophysiology of NAFLD-related HCC has not been completely understood recently.
We analyzed the hub genes related to NAFLD and HCC to predict the risk of NAFLD progressing to HCC.
Two datasets of NAFLD were used to identify differentially expressed genes. Lasso-Cox regression analysis was performed to determine a gene model to predict the risk of the progression from NAFLD to HCC. Three validation datasets were analyzed to evaluate the performance of the gene model, including normal and NAFLD with fibrosis, NAFLD with fibrosis and NAFLD-related HCC, and normal and NASH-related HCC.
Seven genes, including COL1A1, TIPM1, VCAN, FOS, CD79A, CXCL9, and VWF, were identified as the hub genes, and then a gene model was constructed. By calculating, the area under the receiver operating characteristic curves (AUCs) for risk prediction were 0.97, 0.886, and 0.751 in the three validation datasets, respectively. Gene set enrichment analysis indicated that the MAPK, TGFβ, p53, PPAR, insulin signaling pathways, and fatty acid metabolism were significantly upregulated in the high-risk group. GTPase activity and intrinsic apoptotic signaling pathway had significant upregulation in the low-risk group.
The seven hub genes may predict the risk of NAFLD developing into HCC by mediating the potential molecular mechanism, which could be used as biomarkers for predicting the progression, diagnosis, and treatment of NAFLD.
非酒精性脂肪性肝病（NAFLD）是全球慢性肝病最常见的病因。随着患者数量的增加，NAFLD已被确定为肝细胞癌（HCC）的危险因素。最近，NAFLD相关HCC的确切病理生理学尚未完全明确。
我们分析了与NAFLD和HCC相关的枢纽基因，以预测NAFLD进展为HCC的风险。
使用两个NAFLD数据集来鉴定差异表达基因。进行Lasso-Cox回归分析以确定预测从NAFLD进展为HCC风险的基因模型。分析三个验证数据集以评估基因模型的性能，包括正常和纤维化NAFLD、纤维化NAFLD和NAFLD相关HCC，以及正常和NASH相关HCC。
鉴定出包括COL1A1、TIPM1、VCAN、FOS、CD79A、CXCL9和VWF在内的7个基因作为枢纽基因，然后构建了一个基因模型。通过计算，三个验证数据集中风险预测的受试者工作特征曲线下面积（AUC）分别为0.97、0.886和0.751。基因集富集分析表明，高危组中MAPK、TGFβ、p53、PPAR、胰岛素信号通路和脂肪酸代谢显著上调。低危组中GTPase活性和内在凋亡信号通路显著上调。
这7个枢纽基因可能通过介导潜在的分子机制预测NAFLD发展为HCC的风险，可作为预测NAFLD进展、诊断和治疗的生物标志物。
