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Validation of four candidate pancreatic cancer serological biomarkers that improve the performance of CA19.9.

ABSTRACT: The identification of new serum biomarkers with high sensitivity and specificity is an important priority in pancreatic cancer research. Through an extensive proteomics analysis of pancreatic cancer cell lines and pancreatic juice, we previously generated a list of candidate pancreatic cancer biomarkers. The present study details further validation of four of our previously identified candidates: regenerating islet-derived 1 beta (REG1B), syncollin (SYCN), anterior gradient homolog 2 protein (AGR2), and lysyl oxidase-like 2 (LOXL2).The candidate biomarkers were validated using enzyme-linked immunosorbent assays in two sample sets of serum/plasma comprising a total of 432 samples (Sample Set A: pancreatic ductal adenocarcinoma (PDAC, n?=?100), healthy (n?=?92); Sample Set B: PDAC (n?=?82), benign (n?=?41), disease-free (n?=?47), other cancers (n?=?70)). Biomarker performance in distinguishing PDAC from each control group was assessed individually in the two sample sets. Subsequently, multiparametric modeling was applied to assess the ability of all possible two and three marker panels in distinguishing PDAC from disease-free controls. The models were generated using sample set B, and then validated in Sample Set A.Individually, all markers were significantly elevated in PDAC compared to healthy controls in at least one sample set (p???0.01). SYCN, REG1B and AGR2 were also significantly elevated in PDAC compared to benign controls (p???0.01), and AGR2 was significantly elevated in PDAC compared to other cancers (p?

SUBMITTER: Makawita S

PROVIDER: S-EPMC3847832 | biostudies-other | 2013 Sep

REPOSITORIES: biostudies-other

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Validation of four candidate pancreatic cancer serological biomarkers that improve the performance of CA19.9.

Makawita Shalini S Dimitromanolakis Apostolos A Soosaipillai Antoninus A Soleas Ireena I Chan Alison A Gallinger Steven S Haun Randy S RS Blasutig Ivan M IM Diamandis Eleftherios P EP

BMC cancer 20130903

<h4>Background</h4>The identification of new serum biomarkers with high sensitivity and specificity is an important priority in pancreatic cancer research. Through an extensive proteomics analysis of pancreatic cancer cell lines and pancreatic juice, we previously generated a list of candidate pancreatic cancer biomarkers. The present study details further validation of four of our previously identified candidates: regenerating islet-derived 1 beta (REG1B), syncollin (SYCN), anterior gradient ho ...[more]

PMID: 24007603

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Project description:Introduction:The diagnosis of rheumatoid arthritis (RA) is based on a combined approach that includes serological markers such as rheumatoid factor (RF) and anti-citrullinated peptide/protein antibodies (ACPA). The goal of this study was to evaluate the clinical performance of several RF and ACPA immunoassays for the diagnosis of RA, as well as the diagnostic value of a combinatory approach with these markers. Methods:The study cohort included 1,655 patients from the Swiss Clinical Quality Management registry with sera from 968 patients with RA and 687 disease controls, including patients with axial spondyloarthritis (n?=?450) and psoriatic arthritis (n?=?237). ACPA were determined by anti-CCP2 IgG enzyme-linked immunosorbent assay (ELISA), QUANTA Flash® CCP3 IgG [chemiluminescent immunoassay (CIA)], and QUANTA Lite® CCP3 IgG ELISA. RF was determined by ELISA (QUANTA Lite® RF IgM, RF IgA, and RF IgG) and with two research use only CIAs (QUANTA Flash® RF IgM and RF IgA). Results:All three ACPA assays showed good discrimination between RA patients and controls and good clinical performance. Overall, CCP3 performed better than CCP2. More pronounced differences were observed between the RF assays. We observed that CIA platforms for both RF IgM and RF IgA showed better performance than the ELISA platforms. Excellent and good total agreements were found between ELISA and CIA for CCP3 (total agreement 95.3%, kappa?=?0.90), and between CCP2 and CCP3 ELISA (total agreement 86.6%, kappa?=?0.73), respectively. RF IgM CIA and ELISA had a good qualitative agreement (86.5%, kappa?=?0.73); RF IgA CIA and ELISA showed a moderate total agreement (78.5%, kappa?=?0.53). When combinatory analyses were performed, the likelihood of RA increased with dual positivity and triple positivity and combining different markers resulted in higher odds ratio than the individual markers in all cases. Conclusion:ACPA and RF showed good clinical performance in this large Swiss cohort of RA patients and controls. Overall, the performance of CCP3 was superior to CCP2. The combination of these biomarkers in an interval model represents a potential tool for the diagnosis of RA patients.

Dataset Information

Validation of four candidate pancreatic cancer serological biomarkers that improve the performance of CA19.9.

Publications

Validation of four candidate pancreatic cancer serological biomarkers that improve the performance of CA19.9.

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