PMID- 30674322 OWN - NLM STAT- MEDLINE DCOM- 20200401 LR - 20200401 IS - 1479-5876 (Electronic) IS - 1479-5876 (Linking) VI - 17 IP - 1 DP - 2019 Jan 24 TI - Serum protein signature of coronary artery disease in type 2 diabetes mellitus. PG - 17 LID - 10.1186/s12967-018-1755-5 [doi] LID - 17 AB - BACKGROUND: Coronary artery disease (CAD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The purpose of the present study was to discriminate the Indian CAD patients with or without T2DM by using multiple pathophysiological biomarkers. METHODS: Using sensitive multiplex protein assays, we assessed 46 protein markers including cytokines/chemokines, metabolic hormones, adipokines and apolipoproteins for evaluating different pathophysiological conditions of control, T2DM, CAD and T2DM with CAD patients (T2DM_CAD). Network analysis was performed to create protein-protein interaction networks by using significantly (p < 0.05) altered protein markers in each disease using STRING 10.5 database. We used two supervised analysis methods i.e., between class analysis (BCA) and principal component analysis (PCA) to reveals distinct biomarkers profiles. Further, random forest classification (RF) was used to classify the diseases by the panel of markers. RESULTS: Our two supervised analysis methods BCA and PCA revealed a distinct biomarker profiles and high degree of variability in the marker profiles for T2DM_CAD and CAD. Thereafter, the present study identified multiple potential biomarkers to differentiate T2DM, CAD, and T2DM_CAD patients based on their relative abundance in serum. RF classified T2DM based on the abundance patterns of nine markers i.e., IL-1beta, GM-CSF, glucagon, PAI-I, rantes, IP-10, resistin, GIP and Apo-B; CAD by 14 markers i.e., resistin, PDGF-BB, PAI-1, lipocalin-2, leptin, IL-13, eotaxin, GM-CSF, Apo-E, ghrelin, adipsin, GIP, Apo-CII and IP-10; and T2DM _CAD by 12 markers i.e., insulin, resistin, PAI-1, adiponectin, lipocalin-2, GM-CSF, adipsin, leptin, Apo-AII, rantes, IL-6 and ghrelin with respect to the control subjects. Using network analysis, we have identified several cellular network proteins like PTPN1, AKT1, INSR, LEPR, IRS1, IRS2, IL1R2, IL6R, PCSK9 and MYD88, which are responsible for regulating inflammation, insulin resistance, and atherosclerosis. CONCLUSION: We have identified three distinct sets of serum markers for diabetes, CAD and diabetes associated with CAD in Indian patients using nonparametric-based machine learning approach. These multiple marker classifiers may be useful for monitoring progression from a healthy person to T2DM and T2DM to T2DM_CAD. However, these findings need to be further confirmed in the future studies with large number of samples. FAU - Adela, Ramu AU - Adela R AD - Drug Discovery Research Center, Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, 121001, India. AD - Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research, NIPER, Guwahati, Assam, India. FAU - Reddy, Podduturu Naveen Chander AU - Reddy PNC AD - Mediciti Institute of Medical Sciences, Medchal Mandal, Ranga Reddy Dist., Ghanpur, Telangana, India. FAU - Ghosh, Tarini Shankar AU - Ghosh TS AD - Centre for Human Microbial Ecology, Translational Health Science and Technology Institute, Faridabad, 121001, India. FAU - Aggarwal, Suruchi AU - Aggarwal S AD - Drug Discovery Research Center, Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, 121001, India. FAU - Yadav, Amit Kumar AU - Yadav AK AD - Drug Discovery Research Center, Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, 121001, India. FAU - Das, Bhabatosh AU - Das B AD - Centre for Human Microbial Ecology, Translational Health Science and Technology Institute, Faridabad, 121001, India. FAU - Banerjee, Sanjay K AU - Banerjee SK AUID- ORCID: 0000-0002-0008-0480 AD - Drug Discovery Research Center, Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, 121001, India. skbanerjee@thsti.res.in. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190124 PL - England TA - J Transl Med JT - Journal of translational medicine JID - 101190741 RN - 0 (Biomarkers) RN - 0 (Blood Proteins) SB - IM MH - Adult MH - Aged MH - Algorithms MH - Area Under Curve MH - Biomarkers/blood MH - Blood Proteins/*metabolism MH - Case-Control Studies MH - Coronary Artery Disease/*blood/*complications MH - Diabetes Mellitus, Type 2/*blood/*complications MH - Female MH - Humans MH - Machine Learning MH - Male MH - Middle Aged MH - Principal Component Analysis MH - Signal Transduction PMC - PMC6345069 OTO - NOTNLM OT - Adipokines OT - Apolipoproteins OT - Coronary artery diseases OT - Cytokines/chemokines OT - Metabolic hormones and biomarkers OT - Type 2 diabetes mellitus EDAT- 2019/01/25 06:00 MHDA- 2020/04/02 06:00 PMCR- 2019/01/24 CRDT- 2019/01/25 06:00 PHST- 2018/09/06 00:00 [received] PHST- 2018/12/21 00:00 [accepted] PHST- 2019/01/25 06:00 [entrez] PHST- 2019/01/25 06:00 [pubmed] PHST- 2020/04/02 06:00 [medline] PHST- 2019/01/24 00:00 [pmc-release] AID - 10.1186/s12967-018-1755-5 [pii] AID - 1755 [pii] AID - 10.1186/s12967-018-1755-5 [doi] PST - epublish SO - J Transl Med. 2019 Jan 24;17(1):17. doi: 10.1186/s12967-018-1755-5.