The underlying pathophysiology association between the Type 2-diabetic and hepatocellular carcinoma
The underlying pathophysiology association between the Type 2-diabetic and hepatocellular carcinoma
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DOI：
10.1002/jcp.27919
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发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
Tang, Qianli
中科院分区：
文献类型：
--
作者：
Wei, Huamei;Wang, Jianchu;Tang, Qianli
据报道，2型糖尿病（T2 D）疾病会增加肝癌的发病率，然而，其潜在的病理生理机制仍不完全清楚。本研究旨在揭示T2 D与肝细胞癌（HCC）之间的潜在病理生理学联系，从而寻找HCC发生发展过程中可能的治疗靶点。T2 D和HCC的甲基化微阵列数据提取自Gene Expression Omnibus和The Cancer Genome Atlas。在T2 D样本和对照组之间共鉴定了504个差异甲基化基因（DMG），而在HCC样本和对照组之间鉴定了6269个DMG。糖尿病和肝癌共存在336个DMG基因，其中86个为共甲基化基因。这些基因主要富集在糖胺聚糖生物合成途径、脂肪酸途径和糖胺聚糖降解途径以及硫胺素、果糖和甘露糖代谢途径。T2 D DMG和HCC DMG之间存在250个差异甲基化方向的DMG，这些基因通过自然杀伤细胞介导的细胞毒性和ak-STAT信号通路富集在鞘脂代谢途径和免疫途径中。发现8个基因与糖尿病和肝癌的发生发展相关。蛋白质相互作用网络分析结果显示，CDKN 1A基因与肝癌的预后有关。综上所述，发现8个基因与HCC的发生相关，CDKN 1A可能作为HCC的潜在预后基因。
Type 2-diabetic (T2D) disease has been reported to increase the incidence of liver cancer, however, the underlying pathophysiology is still not fully understood. Here, we aimed to reveal the underlying pathophysiology association between the T2D and hepatocellular carcinoma (HCC) and, therefore, to find the possible therapeutic targets in the occurrence and development of HCC. The methylation microarray data of T2D and HCC were extracted from the Gene Expression Omnibus and The Cancer Genome Atlas. A total of 504 differentially methylated genes (DMGs) between T2D samples and the controls were identified, whereas 6269 DMGs were identified between HCC samples and the control groups. There were 336 DMGs coexisting in diabetes and HCC, among which 86 genes were comethylated genes. These genes were mostly enriched in pathways as glycosaminoglycan biosynthesis, fatty acid, and metabolic pathway as glycosaminoglycan degradation and thiamine, fructose and mannose. There were 250 DMGs that had differential methylation direction between T2D DMGs and HCC DMGs, and these genes were enriched in the Sphingolipid metabolism pathway and immune pathways through natural killer cell-mediated cytotoxicity and ak-STAT signaling pathway. Eight genes were found related to the occurrence and development of diabetes and HCC. Moreover, the result of protein-protein interaction network showed that CDKN1A gene was related to the prognosis of HCC. In summary, eight genes were found to be associated with the development of HCC and CDKN1A may serve as the potential prognostic gene for HCC.