Prediagnostic serum biomarkers as early detection tools for pancreatic cancer in a large prospective cohort study

Nolen, BM and Brand, RE and Prosser, D and Velikokhatnaya, L and Allen, PJ and Zeh, HJ and Grizzle, WE and Lomakin, A and Lokshin, AE (2014) Prediagnostic serum biomarkers as early detection tools for pancreatic cancer in a large prospective cohort study. PLoS ONE, 9 (4).

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Abstract

Background: The clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools. Methods: Sixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Results: The panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were significantly altered in sera obtained from cases greater than 1 year prior to diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively associated with time to diagnosis. A training/validation study using alternate halves of the PLCO set failed to identify a biomarker panel with significantly improved performance over CA 19-9 alone. When the entire PLCO set was used for training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1 provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in samples collected <1 and >1 year prior to diagnosis, respectively, compared to SN levels of 25.7% and 17.2% for CA 19-9 alone. Conclusions: Most biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combinations offered advantage over CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis. However, the efficacy of biomarker-based tools remains limited at present. Several biomarkers demonstrated significant velocity related to time to diagnosis, an observation which may offer considerable potential for enhancements in early detection. © 2014 Nolen et al.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Nolen, BM bmn9@pitt.edu BMN9 Brand, RE reb53@pitt.edu REB53 Prosser, D dcp12@pitt.edu DCP12 Velikokhatnaya, L liv1@pitt.edu LIV1 Allen, PJ Zeh, HJ hjz1@pitt.edu HJZ1 Grizzle, WE Lomakin, A Lokshin, AE lokshina@pitt.edu LOKSHINA
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Real, Francisco X. UNSPECIFIED UNSPECIFIED UNSPECIFIED
Date:	18 April 2014
Date Type:	Publication
Journal or Publication Title:	PLoS ONE
Volume:	9
Number:	4
DOI or Unique Handle:	10.1371/journal.pone.0094928
Schools and Programs:	School of Medicine > Medicine School of Medicine > Obstetrics, Gynecology, and Reproductive Sciences School of Medicine > Pathology School of Medicine > Surgery
Refereed:	Yes
Date Deposited:	23 Jun 2014 21:00
Last Modified:	02 Feb 2019 17:55
URI:	http://d-scholarship.pitt.edu/id/eprint/21998

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