Zhao Kang, Mao Rui, Yi Wei, Ren Zhengyun, Liu Yanjun, Yang Huawu, Wang Senlin, Feng Zhonghui
Section for Day Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiao Tong University, Chengdu, 610031, People's Republic of China.
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Diabetes Metab Syndr Obes. 2024 Aug 1;17:2923-2934. doi: 10.2147/DMSO.S467950. eCollection 2024.
AIM/INTRODUCTION: Type 2 diabetes mellitus (T2DM) is one of the most frequent and widespread disease in the world.Obesity is the most significant predictor of T2DM, but the exact mechanism how obesity promotes T2DM remains unknown. Finding specific biomarkers to assist in diagnosing and treating patients with obese and T2DM is critical.
We collected liver tissues from obesity patients with and without T2DM for proteomic sequencing and immunohistochemistry assay. Analysis Gene Ontology(GO) enrichment, Kyoto Encyclopedia of Genes and Genomes(KEGG), and protein interaction network (PPI) were performed on the parameters and data derived from the Tandem Mass Tags(TMT)-based proteomics analysis of liver tissues. Transcriptome data were downloaded from the Gene Expression Omnibus(GEO)website and genes that are deferentially expressed in both transcriptome and proteome were selected.
We identified 140 deferentially expressed proteins from proteomic sequencing. Six biomarkers were deferentially expressed in both proteome and transcriptome with consistent changes in direction. The protein-protein interaction (PPI) analysis suggested CMPK1, the expression with greatest difference, was the core protein among the six biomarkers. Immunohistochemistry validated CMPK1 was upregulated significantly in the liver tissues of T2DM patients. The correlation analysis revealed that the expression of CMPK1 was significantly associated with key molecules in T2DM-related pathways at both protein and transcriptome levels.
Our study showed CMPK1 was upregulated in the liver of T2DM patients and provides a possible new target for screening and diagnosing T2DM in patients with obese and a novel theoretical basis for the pathophysiological mechanism of obesity-related metabolic diseases.
目的/引言：2型糖尿病（T2DM）是世界上最常见且分布广泛的疾病之一。肥胖是T2DM最重要的预测因素，但肥胖促进T2DM的确切机制仍不清楚。寻找特定生物标志物以协助诊断和治疗肥胖及T2DM患者至关重要。
我们收集了患有和未患有T2DM的肥胖患者的肝脏组织，用于蛋白质组测序和免疫组织化学分析。对基于串联质谱标签（TMT）的肝脏组织蛋白质组学分析得出的参数和数据进行基因本体论（GO）富集分析、京都基因与基因组百科全书（KEGG）分析以及蛋白质相互作用网络（PPI）分析。从基因表达综合数据库（GEO）网站下载转录组数据，并选择在转录组和蛋白质组中均差异表达的基因。
我们从蛋白质组测序中鉴定出140种差异表达蛋白。六种生物标志物在蛋白质组和转录组中均差异表达，且变化方向一致。蛋白质-蛋白质相互作用（PPI）分析表明，差异最大的表达蛋白CMPK1是六种生物标志物中的核心蛋白。免疫组织化学验证了CMPK1在T2DM患者肝脏组织中显著上调。相关性分析表明，CMPK1的表达在蛋白质和转录组水平上均与T2DM相关途径中的关键分子显著相关。
我们的研究表明CMPK1在T2DM患者肝脏中上调，为肥胖患者T2DM的筛查和诊断提供了一个可能的新靶点，并为肥胖相关代谢疾病的病理生理机制提供了新的理论基础。
