Shi Zhan, Xiao Zunqiang, Hu Linjun, Gao Yuling, Zhao Junjun, Liu Yang, Shen Guoliang, Xu Qiuran, Huang Dongsheng
The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310014, China.
The Medical College of Qingdao University, Qingdao 266071, China.
Ann Transl Med. 2020 Mar;8(6):380. doi: 10.21037/atm.2020.02.13.
Type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC) are both major health problems throughout the world. It has been reported that T2DM is an independent risk factor for HCC, although the pathophysiology is still unclear.
In order to identify differentially expressed genes (DEGs) in T2DM and HCC, gene expression datasets for T2DM (GSE15653), HCC (GSE60502) and metformin-treated cells (GSE69850) were obtained from the Gene Expression Omnibus database repository. Protein-protein interaction (PPI) networks for the DEGs were constructed and gene clusters selected for functional enrichment analysis. Ten genes with the highest degree of connectivity were selected as hub genes and prognostic analysis together with analysis of gene expression and protein distribution were performed for these genes. Lastly, we investigated associations between the hub genes and genes associated with metformin treatment in hepatocarcinoma cells.
In total, 256 common DEGs, including 155 up-regulated genes and 101 down-regulated genes, were identified. Enrichment analyses showed that the genes of the major module were largely associated with the cell cycle. All of the 10 hub genes ( and ) have a strong association with lower overall survival in liver cancer patients and four genes ( and ) have reduced expression in metformin-treated samples.
This study identified a number of genes that may play important roles in the association of T2DM and HCC, including four genes which may be the target of metformin treatment for diabetes and HCC. The specific mechanisms involved remain to be identified.
2型糖尿病（T2DM）和肝细胞癌（HCC）都是全球范围内的主要健康问题。据报道，T2DM是HCC的独立危险因素，但其病理生理学仍不清楚。
为了鉴定T2DM和HCC中差异表达的基因（DEG），从基因表达综合数据库中获取了T2DM（GSE15653）、HCC（GSE60502）和二甲双胍处理细胞（GSE69850）的基因表达数据集。构建了DEG的蛋白质-蛋白质相互作用（PPI）网络，并选择基因簇进行功能富集分析。选择连接度最高的10个基因作为枢纽基因，并对这些基因进行预后分析以及基因表达和蛋白质分布分析。最后，我们研究了枢纽基因与肝癌细胞中与二甲双胍治疗相关基因之间的关联。
总共鉴定出256个常见的DEG，包括155个上调基因和101个下调基因。富集分析表明，主要模块的基因在很大程度上与细胞周期相关。所有10个枢纽基因（和）都与肝癌患者较低的总生存率密切相关，并且有4个基因（和）在二甲双胍处理的样本中表达降低。
本研究鉴定出了一些可能在T2DM与HCC的关联中起重要作用的基因，包括4个可能是糖尿病和HCC二甲双胍治疗靶点的基因。具体涉及的机制仍有待确定。
