Lin Yuxi, Liao Jiasheng, Chong Yutian
Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, China.
Clin Exp Hepatol. 2025 Mar;11(1):34-44. doi: 10.5114/ceh.2025.148439. Epub 2025 Mar 13.
Type 2 diabetes mellitus (T2DM) is closely related to hepatocellular carcinoma (HCC). The pathophysiological mechanism of coexistence of T2DM and HCC is unclear. The study aimed to investigate the core genes and pathways involved in the development and progression of T2DM and HCC.
Datasets for T2DM and HCC were downloaded from the GEO to screen differentially expressed genes (DEGs). Protein-protein interaction (PPI) network analysis was performed on these DEGs to explore their functions and verify hub genes. These genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR) and UALCAN analysis based on The Cancer Genome Atlas (TCGA). Finally, the transcription factor (TF)-miRNA-target gene network was constructed with hub genes, and visualized using Cytoscape software 3.6.1.
A total of 77 common DEGs were identified. KEGG enrichment revealed that pathways of metabolic processes are enriched in T2DM and HCC. Combining the results of MCODE and CytoHubba showed that , , , and were hub genes. Then, we verified the above results by UALCAN analysis and qRT-PCR. Compared with normal liver tissues, the expression levels of 5 hub genes based on tumor grade were lower in liver hepatocellular carcinoma (LIHC) tissues. mRNA levels of these genes were significantly down-regulated in HepG2 and SNU-449 compared with LO2 cells. Furthermore, we depicted the TF-miRNA-gene interaction network.
This study proposed a strategy for exploring pathogenic mechanisms of T2DM and HCC. Network hub genes hold promise as disease status biomarkers and treatment targets for alleviating both T2DM and HCC.
2型糖尿病（T2DM）与肝细胞癌（HCC）密切相关。T2DM和HCC共存的病理生理机制尚不清楚。本研究旨在探讨参与T2DM和HCC发生发展的核心基因和通路。
从基因表达综合数据库（GEO）下载T2DM和HCC的数据集，以筛选差异表达基因（DEGs）。对这些DEGs进行蛋白质-蛋白质相互作用（PPI）网络分析，以探索其功能并验证枢纽基因。这些基因通过定量实时聚合酶链反应（qRT-PCR）和基于癌症基因组图谱（TCGA）的UALCAN分析进行验证。最后，用枢纽基因构建转录因子（TF）-微小RNA（miRNA）-靶基因网络，并使用Cytoscape软件3.6.1进行可视化。
共鉴定出77个常见的DEGs。京都基因与基因组百科全书（KEGG）富集分析显示，代谢过程通路在T2DM和HCC中富集。结合分子复合物检测（MCODE）和CytoHubba的结果表明， 、 、 、 和 是枢纽基因。然后，我们通过UALCAN分析和qRT-PCR验证了上述结果。与正常肝组织相比，基于肿瘤分级的5个枢纽基因在肝细胞癌（LIHC）组织中的表达水平较低。与LO2细胞相比，这些基因在HepG2和SNU-449细胞中的mRNA水平显著下调。此外，我们描绘了TF-miRNA-基因相互作用网络。
本研究提出了一种探索T2DM和HCC致病机制的策略。网络枢纽基因有望作为疾病状态生物标志物和缓解T2DM和HCC的治疗靶点。
