Zhang Zunni, Zhang Yalong, Mo Wuning
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Ultrasonic Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Front Oncol. 2021 Jan 26;10:626175. doi: 10.3389/fonc.2020.626175. eCollection 2020.
The role of autophagy in tumors is complex; based on known interactions between autophagy and hepatocellular carcinoma (HCC) pathogenesis, we hypothesized that autophagy-related genes (ARGs) may play an important role in HCC. The ARGs were obtained from the Human Autophagy Database and the Gene Set Enrichment Analysis. Based on the area under the curve (AUC) value >0.9 with p <0.0001 and Student's T-test analysis with p <0.0001, differently expressed autophagy-related genes (DEARGs) with high diagnostic efficiency were found. Besides that, we searched in the PubMed database to find novel DEARGs associated with HCC. Then the DEARGs were validated in the GSE25097, GSE54236, GSE76427, GSE64041, Oncomine, and Human Protein Atlas datasets. Finally, survival analysis of CHAF1B in HCC and correlations of clinico-pathological characteristics and CHAF1B were performed based on the TCGA database. The mRNA and protein expression of 531 ARGs were analyzed and validated in eight independent cohorts. First, 18 DEARGs with high diagnostic efficiency were selected from the TCGA database, and nine of them were identified that had not previously been associated with HCC. These nine DEARGs were validated in the GSE25097, GSE54236, GSE76427, GSE64041, Oncomine, and Human Protein Atlas datasets. Additionally, we found that CHAF1B was associated with overall survival and relapse free survival at one, three, and five years. Furthermore, the univariate and multivariate Cox analyses revealed that the high expression of CHAF1B was an independent risk factor in HCC patients. This research demonstrated that CHAF1B was a novel diagnostic and prognostic signature biomarker that could be potentially useful for predicting the development of HCC and may provide new insights for HCC tumorigenesis and treatments.
自噬在肿瘤中的作用是复杂的；基于自噬与肝细胞癌（HCC）发病机制之间已知的相互作用，我们推测自噬相关基因（ARG）可能在HCC中发挥重要作用。这些ARG是从人类自噬数据库和基因集富集分析中获得的。基于曲线下面积（AUC）值>0.9且p<0.0001以及p<0.0001的学生t检验分析，发现了具有高诊断效率的差异表达自噬相关基因（DEARG）。除此之外，我们在PubMed数据库中搜索以找到与HCC相关的新DEARG。然后在GSE25097、GSE54236、GSE76427、GSE64041、Oncomine和人类蛋白质图谱数据集中对这些DEARG进行验证。最后，基于TCGA数据库对HCC中的CHAF1B进行生存分析以及临床病理特征与CHAF1B的相关性分析。对531个ARG的mRNA和蛋白质表达在八个独立队列中进行了分析和验证。首先，从TCGA数据库中选择了18个具有高诊断效率的DEARG，其中9个被鉴定为以前未与HCC相关联。这9个DEARG在GSE25097、GSE54236、GSE76427、GSE64041、Oncomine和人类蛋白质图谱数据集中得到验证。此外，我们发现CHAF1B与1年、3年和5年的总生存期和无复发生存期相关。此外，单变量和多变量Cox分析显示，CHAF1B的高表达是HCC患者的独立危险因素。这项研究表明，CHAF1B是一种新型的诊断和预后特征生物标志物，可能对预测HCC的发展有用，并可能为HCC的肿瘤发生和治疗提供新的见解。
