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

Authors

Hong Peng
Sheng Pan
Yuanqing Yan
Randall E Brand
Gloria M Petersen
Suresh T Chari
Lisa A Lai
Jimmy K Eng
Teresa A Brentnall
Ru Chen

Publication Date

6-11-2020

Journal

Cancers

DOI

10.3390/cancers12061534

PMID

32545216

PMCID

PMC7352938

PubMedCentral® Posted Date

6-11-2020

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

proteomics, pancreatic cancer, pancreatic ductal adenocarcinoma, diabetes, mass spectrometry, plasma, biomarker

Abstract

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.

Comments

Associated Data