PMID- 38402348 OWN - NLM STAT- MEDLINE DCOM- 20240226 LR - 20240427 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 14 IP - 1 DP - 2024 Feb 24 TI - Biomarker screening using integrated bioinformatics for the development of "normal-impaired glucose intolerance-type 2 diabetes mellitus". PG - 4558 LID - 10.1038/s41598-024-55199-y [doi] LID - 4558 AB - Type 2 diabetes mellitus (T2DM) is a progressive disease. We utilized bioinformatics analysis and experimental research to identify biomarkers indicative of the progression of T2DM, aiming for early detection of the disease and timely clinical intervention. Integrating Mfuzz analysis with differential expression analysis, we identified 76 genes associated with the progression of T2DM, which were primarily enriched in signaling pathways such as apoptosis, p53 signaling, and necroptosis. Subsequently, using various analytical methods, including machine learning, we further narrowed down the hub genes to STK17A and CCT5. Based on the hub genes, we calculated the risk score for samples and interestingly found that the score correlated with multiple programmed cell death (PCD) pathways. Animal experiments revealed that the diabetes model exhibited higher levels of MDA and LDH, with lower expression of SOD, accompanied by islet cell apoptosis. In conclusion, our study suggests that during the progression of diabetes, STK17A and CCT5 may contribute to the advancement of the disease by regulating oxidative stress, programmed cell death pathways, and critical signaling pathways such as p53 and MAPK, thereby promoting the death of islet cells. This provides substantial evidence in support of further disease prevention and treatment strategies. CI - (c) 2024. The Author(s). FAU - Luo, Dongqiang AU - Luo D AD - Guangzhou University of Chinese Medicine, Guangzhou, 510000, China. FAU - Gao, Xiaolu AU - Gao X AD - Guangzhou University of Chinese Medicine, Guangzhou, 510000, China. FAU - Zhu, Xianqiong AU - Zhu X AD - Guangzhou University of Chinese Medicine, Guangzhou, 510000, China. FAU - Xu, Jiongbo AU - Xu J AD - Guangzhou University of Chinese Medicine, Guangzhou, 510000, China. FAU - Gao, Pengfei AU - Gao P AD - Yunkang School of Medicine and Health, Nanfang College Guangzhou, Guangzhou, 510000, China. FAU - Zou, Jiayi AU - Zou J AD - Guangzhou University of Chinese Medicine, Guangzhou, 510000, China. FAU - Fan, Qiaoming AU - Fan Q AD - Foshan Hospital of Traditional Chinese Medicine, Foshan, 528000, China. FAU - Xu, Ying AU - Xu Y AD - Guangzhou University of Chinese Medicine, Guangzhou, 510000, China. FAU - Liu, Tian AU - Liu T AD - Foshan Hospital of Traditional Chinese Medicine, Foshan, 528000, China. liutianfzy@163.com. LA - eng GR - grant no. 20202A011031/Guangzhou Health Science and Technology Project/ PT - Journal Article DEP - 20240224 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Tumor Suppressor Protein p53) RN - 0 (Biomarkers) SB - IM EIN - Sci Rep. 2024 Apr 25;14(1):9498. PMID: 38664473 MH - Animals MH - *Diabetes Mellitus, Type 2/metabolism MH - *Glucose Intolerance/metabolism MH - Tumor Suppressor Protein p53/genetics MH - Biomarkers MH - Computational Biology PMC - PMC10894242 OTO - NOTNLM OT - Bioinformatics OT - Developmental process OT - Impaired glucose tolerance OT - Oxidative stress OT - Type 2 diabetes COIS- The authors declare no competing interests. EDAT- 2024/02/25 00:42 MHDA- 2024/02/26 06:43 PMCR- 2024/02/24 CRDT- 2024/02/24 23:27 PHST- 2023/07/22 00:00 [received] PHST- 2024/02/21 00:00 [accepted] PHST- 2024/02/26 06:43 [medline] PHST- 2024/02/25 00:42 [pubmed] PHST- 2024/02/24 23:27 [entrez] PHST- 2024/02/24 00:00 [pmc-release] AID - 10.1038/s41598-024-55199-y [pii] AID - 55199 [pii] AID - 10.1038/s41598-024-55199-y [doi] PST - epublish SO - Sci Rep. 2024 Feb 24;14(1):4558. doi: 10.1038/s41598-024-55199-y.