Published online Jun 7, 2015. doi: 10.3748/wjg.v21.i21.6604
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.
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.