Dataset Information

Quantitative Proteomic Analysis of Differentially Expressed Protein Profiles Involved in Pancreatic Ductal Adenocarcinoma.

ABSTRACT:

Objectives

The aim of this study was to identify differentially expressed proteins among various stages of pancreatic ductal adenocarcinoma (PDAC) by shotgun proteomics using nano-liquid chromatography coupled tandem mass spectrometry and stable isotope dimethyl labeling.

Methods

Differentially expressed proteins were identified and compared based on the mass spectral differences of their isotope-labeled peptide fragments generated from protease digestion.

Results

Our quantitative proteomic analysis of the differentially expressed proteins with stable isotope (deuterium/hydrogen ratio, ? 2) identified a total of 353 proteins, with at least 5 protein biomarker proteins that were significantly differentially expressed between cancer and normal mice by at least a 2-fold alteration. These 5 protein biomarker candidates include ?-enolase, ?-catenin, 14-3-3 ?, VDAC1, and calmodulin with high confidence levels. The expression levels were also found to be in agreement with those examined by Western blot and histochemical staining.

Conclusions

The systematic decrease or increase of these identified marker proteins may potentially reflect the morphological aberrations and diseased stages of pancreas carcinoma throughout progressive developments leading to PDAC. The results would form a firm foundation for future work concerning validation and clinical translation of some identified biomarkers into targeted diagnosis and therapy for various stages of PDAC.

SUBMITTER: Kuo KK

PROVIDER: S-EPMC4677599 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Publications

Quantitative Proteomic Analysis of Differentially Expressed Protein Profiles Involved in Pancreatic Ductal Adenocarcinoma.

Kuo Kung-Kai KK Kuo Chao-Jen CJ Chiu Chiang-Yen CY Liang Shih-Shin SS Huang Chun-Hao CH Chi Shu-Wen SW Tsai Kun-Bow KB Chen Chiao-Yun CY Hsi Edward E Cheng Kuang-Hung KH Chiou Shyh-Horng SH

Pancreas 20160101 1

<h4>Objectives</h4>The aim of this study was to identify differentially expressed proteins among various stages of pancreatic ductal adenocarcinoma (PDAC) by shotgun proteomics using nano-liquid chromatography coupled tandem mass spectrometry and stable isotope dimethyl labeling.<h4>Methods</h4>Differentially expressed proteins were identified and compared based on the mass spectral differences of their isotope-labeled peptide fragments generated from protease digestion.<h4>Results</h4>Our quant ...[more]

PMID: 26262590

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Project description:PurposeHypodensity of pancreatic ductal adenocarcinoma (PDAC) during contrast-enhanced computed tomography (CECT) examination is common, but a minority of PDAC patients exhibit hyperdense images. The present study examined the clinical characteristics and protein landscape of PDAC with hyperdensity.Materials and methodsA total of 844 pathologically confirmed PDAC patients who underwent CECT before surgery were included. During the parenchymal phase of CECT, patients were assigned to the hyperdense or hypodense group based on CT values. Clinical and CT characteristics for predicting relapse-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox proportional hazards model. The expression of the tumor angiogenesis marker CD31 and stroma-related protein CTHRC1 were analyzed using immunohistochemistry (IHC) assay to evaluate differences between the two groups. Proteomics was performed to compare the possible mechanisms underlying the differential enhancement on CT scans.ResultsBased on CECT, 43 and 801 PDAC patients had hyperdense and hypodense lesions, respectively. All 43 patients presented a hyperdense lesion in the parenchymal phase. The mean CECT values of the hyperdense group were higher than the hypodense group (102.5 ± 17.4 and 53.7 ± 18.7, respectively, P < 0.001). The hyperdense group had a better prognosis than the hypodense group (median RFS, 19.97 vs. 12.34 months, P = 0.0176; median OS, 33.6 vs. 20.3 months, P = 0.047). Multivariate analysis showed that age, higher CA19-9 levels (> 300 U/ml), tumor stage, tumor differentiation, tumor CT density, and adjuvant chemotherapy were significant independent prognostic factors for OS. CD31 immunohistochemical staining showed that the hyperdense PDACs had a higher microvessel density than the hypodense group (P < 0.001). CTHRC1 expression was higher in the hypodense group (P = 0.019). Sixty-eight differentially expressed proteins were found using the tandem mass tag labeling-based quantification of the proteomes of PDAC tissue samples, and 7 proteins (POFUT1, PKP2, P0DOX4, ITPR1, HBG2, IGLC3, SAA2) were related to angiogenesis.ConclusionPatients who presented with a hyperdense mass on CECT had a higher microvessel density and better prognosis. Anti-angiogenic therapy may be suitable for these patients.

Dataset Information

Quantitative Proteomic Analysis of Differentially Expressed Protein Profiles Involved in Pancreatic Ductal Adenocarcinoma.

Objectives

Methods

Results

Conclusions

Publications

Quantitative Proteomic Analysis of Differentially Expressed Protein Profiles Involved in Pancreatic Ductal Adenocarcinoma.

Similar Datasets

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