Diabetes, Metabolic Syndrome and Obesity (Feb 2024)
Transcriptomic Analysis of Type 2 Diabetes Mellitus Combined with Lower Extremity Atherosclerotic Occlusive Disease
Abstract
Guang Zeng,1,* Yong-Zhi Jin,1,* Yi Huang,1 Jun-Sheng Hu,1 Meng-Fan Li,2 Ming Tian,3 Jun Lu,4 Rong Huang1 1Department of General Surgery, Putuo Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People’s Republic of China; 2Department of General Surgery, LiQun Hospital, Shanghai, 200333, People’s Republic of China; 3Department of Burn, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of China; 4Department of Endocrinology, Putuo Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Lu; Rong Huang, Email [email protected]; [email protected]: The pathological damage mechanism of type 2 diabetes (T2D) and macroangiopathy is extremely complex, and T2D and arteriosclerosis obliterans have different biological behaviors and clinical features. To explore the mechanism of lower extremity arteriosclerosis occlusion (LEAOD) in T2D patients, we utilized RNA-seq to identify unique gene expression signatures of T2D and LEAOD through transcriptomic analysis.Methods: We obtained blood samples and performed RNA sequencing from four patients with T2D, five of whom had LEAOD. Another six age- and gender-matched blood samples from healthy volunteers were used for control. By exploring the general and specific differential expression analysis after transcriptome sequencing, specific gene expression patterns of T2D and LEAOD were verified.Results: Transcriptome analysis found differentially expressed genes in T2D, and T2D + LEAOD (vs normal) separately, of which 35/486 (T2D/T2D + LEAOD) were up-regulated and 1290/2970 (T2D/T2D + LEAOD) were down-regulated. A strong overlap of 571 genes across T2D, LEAOD, and coexisting conditions was mainly involved in extracellular exosomes and the transcription process. By exploring the sex difference gene expression features between T2D, T2D + LEAOD, and healthy controls, we noticed that sex chromosome-associated genes do not participate in the sexual dimorphism gene expression profiles of T2D and LEAOD. Protein–Protein Interaction Network analysis and drug target prediction provided the drug candidates to treat T2D and LEAOD.Conclusion: This study provides some evidence at the transcript level to uncover the association of T2D with LEAOD. The screened hub genes and predicted target drugs may be therapeutic targets.Keywords: type 2 diabetes mellitus, lower extremity arterial disease, gene expression profile, hub gene
