Dataset Information

Identification of Serum Biomarker Panels for the Early Detection of Pancreatic Cancer.

ABSTRACT: BACKGROUND:Pancreatic cancer is a deadly disease for which available biomarkers, such as CA19-9, lack the desired sensitivity and specificity for early detection. Additional biomarkers are needed to improve both its sensitivity and specificity. METHODS:Multiplex immunoassays were developed for selected biomarkers using a Bio-Plex 200 system, and analytical performance was optimized. All proteins were analyzed in sera of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC; n = 188) or benign pancreatic conditions (131) and healthy controls (89). The clinical performance of these markers was evaluated individually or in combination for their ability to complement CA19-9 for the early detection of pancreatic cancer. RESULTS:A 6-plex immunoassay was developed with negligible cross-reactivity, wide dynamic range, recovery of 89% to 104%, and intra-assay and interassay precision of 10.2% to 19.6% and 13.7% to 29.3%, respectively. Individually, the best biomarkers to separate PDAC early stage from chronic pancreatitis or intraductal papillary mucinous neoplasm (IPMN) were CA19-9 and MIA or CA19-9 and MIC-1. Logistic regression modeling selected the two-marker panels that significantly improved the individual biomarker performance in discriminating PDAC early stage from chronic pancreatitis (AUCCA19-9+MIA = 0.86 vs. AUCCA19-9 = 0.81 or AUCMIA = 0.75 only, P < 0.05) or IPMN (AUCCA19-9+MIC-1 = 0.81 vs. AUCCA19-9 = 0.75 or AUCMIC-1 = 0.73 only, P < 0.05). It was observed that osteopontin (OPN) outperformed CA19-9 in separating IPMN from chronic pancreatitis (AUCOPN = 0.80 vs. AUCCA19-9 = 0.70, P < 0.01). CONCLUSIONS:The biomarker panels evaluated by assays with high analytical performance demonstrated potential complementary values to CA19-9, warranting additional clinical validation to determine their role in early detection of pancreatic cancer. IMPACT:The validated biomarker panels could lead to earlier intervention and better outcomes.

SUBMITTER: Song J

PROVIDER: S-EPMC6324978 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Identification of Serum Biomarker Panels for the Early Detection of Pancreatic Cancer.

Song Jin J Sokoll Lori J LJ Pasay Jered J JJ Rubin Abigail L AL Li Hanying H Bach Dylan M DM Chan Daniel W DW Zhang Zhen Z

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20181017 1

<h4>Background</h4>Pancreatic cancer is a deadly disease for which available biomarkers, such as CA19-9, lack the desired sensitivity and specificity for early detection. Additional biomarkers are needed to improve both its sensitivity and specificity.<h4>Methods</h4>Multiplex immunoassays were developed for selected biomarkers using a Bio-Plex 200 system, and analytical performance was optimized. All proteins were analyzed in sera of patients diagnosed with pancreatic ductal adenocarcinoma (PDA ...[more]

PMID: 30333219

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Project description:BackgroundThe prognosis of pancreatic cancer (PC) is one of the poorest among all cancers, due largely to the lack of methods for screening and early detection. New biomarkers for identifying high-risk or early-stage subjects could significantly impact PC mortality. The goal of this study was to find metabolic biomarkers associated with PC by using a comprehensive metabolomics technology to compare serum profiles of PC patients to healthy control subjects.MethodsA non-targeted metabolomics approach based on high-resolution, flow-injection Fourier transform ion cyclotron resonance mass spectrometry (FI-FTICR-MS) was used to generate comprehensive metabolomic profiles containing 2478 accurate mass measurements from the serum of Japanese PC patients (n=40) and disease-free subjects (n=50). Targeted flow-injection tandem mass spectrometry (FI-MS/MS) assays for specific metabolic systems were developed and used to validate the FI-FTICR-MS results. A FI-MS/MS assay for the most discriminating metabolite discovered by FI-FTICR-MS (PC-594) was further validated in two USA Caucasian populations; one comprised 14 PCs, six intraductal papillary mucinous neoplasms (IPMN) and 40 controls, and a second comprised 1000 reference subjects aged 30 to 80, which was used to create a distribution of PC-594 levels among the general population.ResultsFI-FTICR-MS metabolomic analysis showed significant reductions in the serum levels of metabolites belonging to five systems in PC patients compared to controls (all p<0.000025). The metabolic systems included 36-carbon ultra long-chain fatty acids, multiple choline-related systems including phosphatidylcholines, lysophosphatidylcholines and sphingomyelins, as well as vinyl ether-containing plasmalogen ethanolamines. ROC-AUCs based on FI-MS/MS of selected markers from each system ranged between 0.93 ±0.03 and 0.97 ±0.02. No significant correlations between any of the systems and disease-stage, gender, or treatment were observed. Biomarker PC-594 (an ultra long-chain fatty acid), was further validated using an independently-collected US Caucasian population (blinded analysis, n=60, p=9.9E-14, AUC=0.97 ±0.02). PC-594 levels across 1000 reference subjects showed an inverse correlation with age, resulting in a drop in the AUC from 0.99 ±0.01 to 0.90 ±0.02 for subjects aged 30 to 80, respectively. A PC-594 test positivity rate of 5.0% in low-risk reference subjects resulted in a PC sensitivity of 87% and a significant improvement in net clinical benefit based on decision curve analysis.ConclusionsThe serum metabolome of PC patients is significantly altered. The utility of serum metabolite biomarkers, particularly PC-594, for identifying subjects with elevated risk of PC should be further investigated.

Dataset Information

Identification of Serum Biomarker Panels for the Early Detection of Pancreatic Cancer.

Publications

Identification of Serum Biomarker Panels for the Early Detection of Pancreatic Cancer.

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