Case Control Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2015; 21(21): 6604-6612
Published online Jun 7, 2015. doi: 10.3748/wjg.v21.i21.6604
Pancreatic cancer serum biomarker PC-594: Diagnostic performance and comparison to CA19-9
Shawn A Ritchie, Bassirou Chitou, Qingan Zheng, Dushmanthi Jayasinghe, Wei Jin, Asuka Mochizuki, Dayan B Goodenowe
Shawn A Ritchie, Bassirou Chitou, Dushmanthi Jayasinghe, Department of Biomarker Discovery and Validation, Phenomenome Discoveries, Saskatoon, SK S7N 4L8, Canada
Qingan Zheng, Department of Manufacturing, Phenomenome Discoveries, Saskatoon, SK S7N 4L8, Canada
Wei Jin, Asuka Mochizuki, Phenomenome Laboratory Services, Saskatoon, SK S7N 4L8, Canada
Dayan B Goodenowe, Phenomenome Discoveries, Saskatoon, SK S7N 4L8, Canada
Author contributions: Ritchie SA and Goodenowe DB designed the studies and directed the research; Ritchie SA was the primary author, directed the CA19.9 analysis, and analyzed all data; Chitou B performed, reviewed and verified the statistical analyses; Zheng Q and Jayasinghe D performed PC-594 isolation; Jin W and Mochizuki A developed the tandem MS assay and performed the analysis.
Ethics approval: All human biospecimens distributed by Conversant Bio (601 Genome Way Suite 1200, Huntsville, Alabama 35806) were collected, processed, and distributed in full ethical and regulatory compliance with the Sites from which human biospecimens are collected. This includes independent ethical review, Institutional Review Board approval (where appropriate), independent regulatory review, and Conversant Bio ethical review for all of Conversant Bio’s collection Sites. All tissues were obtained within applicable laws.
Informed consent: Samples for this study were obtained commercially from Conversant Bio (601 Genome Way Suite 1200, Huntsville, Alabama 35806). Conversant Bio warrants that a separate patient consent form containing language substantially the same as that which is set forth in the consent form was signed by each patient from whom recipient party received human biospecimens. All patients signed informed consents, and samples were collected under ethics-approved protocols according to the requirements of Conversant Bio.
Conflict-of-interest: All authors of this work received salaries from Phenomenome Discoveries, Inc. during the duration of the project. Dayan Goodenowe is a shareholder of Phenomenome Discoveries, Inc. Shawn Ritchie is listed as inventor relating to the use of PC-594 for identifying pancreatic cancer risk, PCT/CA/2010/001565.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dr. Shawn A Ritchie, Department of Biomarker Discovery and Validation, Phenomenome Discoveries, Inc. 204-407 Downey Road, Saskatoon, SK S7N 4L8, Canada.
Telephone: +1-306-2448233 Fax: +1-306-2446730
Received: January 7, 2015
Peer-review started: January 8, 2015
First decision: January 22, 2015
Revised: February 11, 2015
Accepted: March 19, 2015
Article in press: March 19, 2015
Published online: June 7, 2015

AIM: To investigate serum PC-594 fatty acid levels as a potential biomarker in North American pancreatic cancer (PaC) patients, and to compare its performance to CA19-9.

METHODS: Using tandem mass spectrometry, we evaluated serum PC-594 levels from 84 North American patients with confirmed PaC and 99 cancer-free control subjects. We determined CA19-9 levels by ELISA. Significance between PaC patients and controls, and association with clinical variables was determined by analysis of variance and t-tests. Diagnostic performance was evaluated by receiver-operator characteristic (ROC) curve analysis, and PC-594 correlation with age and CA19-9 determined by regression analysis.

RESULTS: Mean PC-594 levels were 3.7 times lower in PaC patients compared to controls (P < 0.0001). The mean level in PaC patient serum was 0.76 ± 0.07 μmol/L, and the mean level in control subjects was 2.79 ± 0.15 μmol/L. There was no correlation between PC-594 and age, disease stage or gender (P > 0.05). Using 1.25 μmol/L as a PC-594 threshold produced a relative risk (RR) of 9.4 (P < 0.0001, 95%CI: 5.0-17.7). The area under the receiver-operator characteristic curve (ROC-AUC) was 0.93 (95%CI: 0.91-0.95) for PC-594 and 0.85 (95%CI: 0.82-0.88) for CA19-9. Sensitivity at 90% specificity was 87% for PC-594 and 71% for CA19-9. Six PaC patients with CA19-9 above 35 U/mL showed normal PC-594 levels, while 24 PaC patients with normal CA19-9 showed low PC-594 levels. Eighty-five of the 99 control subjects (86%) showed normal levels of both markers.

CONCLUSION: PC-594 biomarker levels are significantly reduced in North American PaC patients, and showed superior diagnostic performance compared to CA19-9.

Keywords: Pancreatic cancer, Risk, Screening, Blood, Fatty acid, Biomarker, Metabolite, PC-594

Core tip: The incidence of pancreatic cancer (PaC) in the general population is too low to warrant screening by imaging or endoscopic ultrasound. In this paper, we provide further validation that the serum fatty acid metabolite PC-594 is a viable PaC biomarker by showing that it is significantly reduced in North American PaC patients compared to control subjects, and that its performance is superior to CA19-9. This reduction represents a near 10-fold increase for PaC risk, and a PaC incidence among PC-594 deficient subjects that exceeds the incidence of colorectal cancer considered sufficient to warrant colonoscopy-based screening. PC-594 therefore represents an opportunity to identify a subset of the general population with high PaC risk.