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Systemic Proteome Alterations Linked to Early Stage Pancreatic Cancer in Diabetic Patients

Peng, Hong and Pan, Sheng and Yan, Yuanqing and Brand, Randall E. and Petersen, Gloria M. and Chari, Suresh T. and Lai, Lisa A. and Eng, Jimmy K. and Brentnall, Teresa A. and Chen, Ru (2020) Systemic Proteome Alterations Linked to Early Stage Pancreatic Cancer in Diabetic Patients. Cancers, 12 (6). p. 1534. ISSN 2072-6694

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Background: Diabetes is a risk factor associated with pancreatic ductal adenocarcinoma (PDAC), and new adult-onset diabetes can be an early sign of pancreatic malignancy. Development of blood-based biomarkers to identify diabetic patients who warrant imaging tests for cancer detection may represent a realistic approach to facilitate earlier diagnosis of PDAC in a risk population. Methods: A spectral library-based proteomic platform was applied to interrogate biomarker candidates in plasma samples from clinically well-defined diabetic cohorts with and without PDAC. Random forest algorithm was used for prediction model building and receiver operating characteristic (ROC) curve analysis was applied to evaluate the prediction probability of potential biomarker panels. Results: Several biomarker panels were cross-validated in the context of detection of PDAC within a diabetic background. In combination with carbohydrate antigen 19-9 (CA19-9), the panel, which consisted of apolipoprotein A-IV (APOA4), monocyte differentiation antigen CD14 (CD14), tetranectin (CLEC3B), gelsolin (GSN), histidine-rich glycoprotein (HRG), inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3), plasma kallikrein (KLKB1), leucine-rich alpha-2-glycoprotein (LRG1), pigment epithelium-derived factor (SERPINF1), plasma protease C1 inhibitor (SERPING1), and metalloproteinase inhibitor 1 (TIMP1), demonstrated an area under curve (AUC) of 0.85 and a two-fold increase in detection accuracy compared to CA19-9 alone. The study further evaluated the correlations of protein candidates and their influences on the performance of biomarker panels. Conclusions: Proteomics-based multiplex biomarker panels improved the detection accuracy for diagnosis of early stage PDAC in diabetic patients.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Peng, Hong
Pan, Sheng
Yan, Yuanqing
Brand, Randall E.reb53@pitt.edureb53
Petersen, Gloria M.
Chari, Suresh T.
Lai, Lisa A.
Eng, Jimmy K.
Brentnall, Teresa A.
Chen, Ru
Date: 11 June 2020
Date Type: Publication
Journal or Publication Title: Cancers
Volume: 12
Number: 6
Publisher: MDPI AG
Page Range: p. 1534
DOI or Unique Handle: 10.3390/cancers12061534
Schools and Programs: School of Medicine > Medicine
Refereed: Yes
Uncontrolled Keywords: proteomics, pancreatic cancer, pancreatic ductal adenocarcinoma, diabetes, mass spectrometry, plasma
ISSN: 2072-6694
Official URL:
Funders: National Institutes of Health
Article Type: Research Article
Date Deposited: 14 Jun 2021 18:54
Last Modified: 14 Jun 2021 18:54


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