Dataset Information

ITRAQ-based quantitative proteomics reveals apolipoprotein A-I and transferrin as potential serum markers in CA19-9 negative pancreatic ductal adenocarcinoma.

ABSTRACT: Currently the diagnosis of pancreatic ductal adenocarcinoma (PDAC) relies on CA19-9 and radiological means, whereas some patients do not have elevated levels of CA19-9 secondary to pancreatic cancer. The purpose of this study was to identify potential serum biomarkers for CA19-9 negative PDAC.A total of 114 serum samples were collected from 3 groups: CA19-9 negative PDAC patients (n?=?34), CA19-9 positive PDAC patients (n?=?44), and healthy volunteers (n?=?36), whereas the first 12 samples from each group were used for isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Thereafter, candidate biomarkers were selected for validation by enzyme-linked immunosorbent assay (ELISA) with the rest specimens.Using the iTRAQ approach, a total of 5 proteins were identified as significantly different between CA19-9 negative PDAC patients and healthy subjects according to our defined criteria. Apolipoprotein A-I (APOA-I) and transferrin (TF) were selected to validate the proteomic results by ELISA in a further 78 serum specimens. It revealed that TF significantly correlated with the degree of histological differentiation (P?=?0.042), and univariate and multivariate analyses indicated that TF is an independent prognostic factor for survival (hazard ratio, 0.302; 95% confidence interval, 0.118-0.774; P?=?0.013) of patients with PDAC after curative surgery.ITRAQ-based quantitative proteomics revealed that APOA-I and TF may be potential CA19-9 negative PDAC serum markers.

SUBMITTER: Lin C

PROVIDER: S-EPMC4979862 | biostudies-other | 2016 Aug

REPOSITORIES: biostudies-other

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ITRAQ-based quantitative proteomics reveals apolipoprotein A-I and transferrin as potential serum markers in CA19-9 negative pancreatic ductal adenocarcinoma.

Lin Chao C Wu Wen-Chuan WC Zhao Guo-Chao GC Wang Dan-Song DS Lou Wen-Hui WH Jin Da-Yong DY

Medicine 20160801 31

Currently the diagnosis of pancreatic ductal adenocarcinoma (PDAC) relies on CA19-9 and radiological means, whereas some patients do not have elevated levels of CA19-9 secondary to pancreatic cancer. The purpose of this study was to identify potential serum biomarkers for CA19-9 negative PDAC.A total of 114 serum samples were collected from 3 groups: CA19-9 negative PDAC patients (n = 34), CA19-9 positive PDAC patients (n = 44), and healthy volunteers (n = 36), whereas the first 12 samples from ...[more]

PMID: 27495108

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Project description:UnlabelledVascular dementia (VaD) is a leading cause of dementia in the elderly together with Alzheimer's disease with limited treatment options. Poor understanding of the pathophysiology underlying VaD is hindering the development of new therapies. Hence, to unravel its underlying molecular pathology, an iTRAQ-2D-LC-MS/MS strategy was used for quantitative analysis of pooled lysates from Brodmann area 21 of pathologically confirmed cases of VaD and matched non-neurological controls. A total of 144 differentially expressed proteins out of 2281 confidently identified proteins (false discovery rate=0.3%) were shortlisted for bioinformatics analysis. Western blot analysis of selected proteins using samples from individual patients (n=10 per group) showed statistically significant increases in the abundance of SOD1 and NCAM and reduced ATP5A in VaD. This suggested a state of hypometabolism and vascular insufficiency along with an inflammatory condition during VaD. Elevation of SOD1 and increasing trend for iron-storage proteins (FTL, FTH1) may be indicative of an oxidative imbalance that is accompanied by an aberrant iron metabolism. The synaptic proteins did not exhibit a generalized decrease in abundance (e.g. syntaxin) in the VaD subjects. This reported proteome offers a reference data set for future basic or translational studies on VaD.Biological significanceOur study is the first quantitative clinical proteomic study where iTRAQ-2D-LC-MS/MS strategy has been used to identify the differential proteome in the VaD cortex by comparing VaD and matched control subjects. We generate testable hypothesis about the involvement of various proteins in the vascular and parenchymal events during the evolution of VaD that finally leads to malfunction and demise of brain cells. This study also establishes quantitative proteomics as a complementary approach and viable alternative to existing neurochemical, electron microscopic and neuroimaging techniques that are traditionally being used to understand the molecular pathology of VaD. Our study could inspire fellow researchers to initiate similar retrospective studies targeting various ethnicities, age-groups or sub-types of VaD using brain samples available from brain banks across the world. Meta-analysis of these studies in the future may be able to shortlist candidate proteins or pathways for rationale exploration of therapeutic targets or biomarkers for VaD.

Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) is an aggressive gastrointestinal cancer characterized by an extremely low survival rate because of early metastasis. Identifying satisfactory therapeutic targets associated with metastasis is crucial to improve the treatment effect of PDAC.Materials and methodsIn this research, we used stable isotope labeling by amino acids in cell culture, 1-dodecyl-3-methylimidazolium chloride-assisted sample preparation method preparing protein sample and nano-reversed-phase liquid chromatography-mass spectrometry/mass spectrometry analysis to perform the comparative proteomics of two homologous hamster pancreatic cancer cell lines that are different in metastatic ability: PC-1.0 (highly metastatic) and PC-1 (weakly metastatic). Verifications are through immunohistochemistry on clinical human PDAC pathologic tissues as well as by Western blot of human pancreatic cancer cell lines. siRNA silencing methods were used to study the effect of molecules on invasion and metastasis of pancreatic cancer cell lines.ResultsBioinformatic analysis indicated that a total of 141 differentially expressed proteins (82 upregulated and 59 downregulated in PC-1.0 cells) were identified showing obviously differential expression (>1.5-fold change). These differentially expressed proteins were involved in a number of different biologic functions, metabolic pathways, and pathophysiologic processes. Phosphoglycerate mutase 1 (PGAM1) and HSPE1 are the top two upregulated proteins, and PDIA3 and CALR are the top two downregulated proteins in PC-1.0 cells compared to PC-1 cells. PGAM1 and HSPE1 showed higher expressions in PDAC tissue with clinical metastasis and highly metastatic pancreatic cancer cell lines PC-1.0 and Aspc-1. PDIA3 and CALR showed higher expressions in weakly metastatic pancreatic cancer cell lines PC-1 and Capan-2. The Western blot results were consistent with the MS quantification data. Silencing PGAM1 was found to decrease the migration and invasion of pancreatic cancer cell lines with statistical significance, especially in highly metastatic PC-1.0 and Aspc-1 cell lines.ConclusionThese data indicated that PGAM1 may be a potential therapeutic target for PDAC metastasis.

Dataset Information

ITRAQ-based quantitative proteomics reveals apolipoprotein A-I and transferrin as potential serum markers in CA19-9 negative pancreatic ductal adenocarcinoma.

Publications

ITRAQ-based quantitative proteomics reveals apolipoprotein A-I and transferrin as potential serum markers in CA19-9 negative pancreatic ductal adenocarcinoma.

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