PMID- 23050762 OWN - NLM STAT- MEDLINE DCOM- 20130425 LR - 20151119 IS - 1535-3907 (Electronic) IS - 1535-3893 (Linking) VI - 11 IP - 11 DP - 2012 Nov 2 TI - iTRAQ-based quantitative protein expression profiling and MRM verification of markers in type 2 diabetes. PG - 5527-39 LID - 10.1021/pr300798z [doi] AB - The pathogenesis of Type 2 diabetes mellitus (T2DM) is complex owing to molecular heterogeneity in the afflicted population. Current diagnostic methods rely on blood glucose measurements, which are noninformative with respect to progression of the disease to other associated pathologies. Thus, predicting the risk and development of T2DM-related complications, such as cardiovascular disease, remains a major challenge. We have used a combination of quantitative methods for characterization of circulating serum biomarkers of T2DM using a cohort of nondiabetic control subjects (n = 76) and patients diagnosed with T2DM (n = 106). In this case-control study, the samples were randomly divided as training and validation data sets. In the first step, iTRAQ (isobaric tagging for relative and absolute quantification) based protein expression profiling was performed for identification of proteins displaying a significant differential expression in the two study groups. Five of these protein markers were selected for validation using multiple reaction-monitoring mass spectrometry (MRM-MS) and further confirmed with Western blot and QPCR analysis. Functional pathway analysis identified perturbations in lipid and small molecule metabolism as well as pathways that lead to disruption of glucose homeostasis and blood coagulation. These putative biomarkers may be clinically useful for subset stratification of T2DM patients as well as for the development of novel therapeutics targeting the specific pathology. FAU - Kaur, Prabhjit AU - Kaur P AD - Department of Oncology, Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, D.C., USA. FAU - Rizk, Nasser M AU - Rizk NM FAU - Ibrahim, Sereen AU - Ibrahim S FAU - Younes, Noura AU - Younes N FAU - Uppal, Arushi AU - Uppal A FAU - Dennis, Kevin AU - Dennis K FAU - Karve, Tejaswita AU - Karve T FAU - Blakeslee, Kenneth AU - Blakeslee K FAU - Kwagyan, John AU - Kwagyan J FAU - Zirie, Mahmoud AU - Zirie M FAU - Ressom, Habtom W AU - Ressom HW FAU - Cheema, Amrita K AU - Cheema AK LA - eng GR - P30-CA051008/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20121023 PL - United States TA - J Proteome Res JT - Journal of proteome research JID - 101128775 RN - 0 (Biomarkers) RN - 0 (Blood Proteins) SB - IM MH - Biomarkers/*blood MH - Blood Proteins/*metabolism MH - Chromatography, Liquid MH - Diabetes Mellitus, Type 2/*blood MH - Humans MH - Real-Time Polymerase Chain Reaction MH - Tandem Mass Spectrometry EDAT- 2012/10/12 06:00 MHDA- 2013/04/26 06:00 CRDT- 2012/10/12 06:00 PHST- 2012/10/12 06:00 [entrez] PHST- 2012/10/12 06:00 [pubmed] PHST- 2013/04/26 06:00 [medline] AID - 10.1021/pr300798z [doi] PST - ppublish SO - J Proteome Res. 2012 Nov 2;11(11):5527-39. doi: 10.1021/pr300798z. Epub 2012 Oct 23.