Identification of a biomarker panel using a multiplex proximity ligation assay improves accuracy of pancreatic cancer diagnosis.
BACKGROUND
Pancreatic cancer continues to prove difficult to clinically diagnose. Multiple simultaneous measurements of plasma biomarkers can increase sensitivity and selectivity of diagnosis. Proximity ligation assay (PLA) is a highly sensitive technique for multiplex detection of biomarkers in plasma with little or no interfering background signal.


METHODS
We examined the plasma levels of 21 biomarkers in a clinically defined cohort of 52 locally advanced (Stage II/III) pancreatic ductal adenocarcinoma cases and 43 age-matched controls using a multiplex proximity ligation assay. The optimal biomarker panel for diagnosis was computed using a combination of the PAM algorithm and logistic regression modeling. Biomarkers that were significantly prognostic for survival in combination were determined using univariate and multivariate Cox survival models.


RESULTS
Three markers, CA19-9, OPN and CHI3L1, measured in multiplex were found to have superior sensitivity for pancreatic cancer vs. CA19-9 alone (93% vs. 80%). In addition, we identified two markers, CEA and CA125, that when measured simultaneously have prognostic significance for survival for this clinical stage of pancreatic cancer (p < 0.003).


CONCLUSIONS
A multiplex panel assaying CA19-9, OPN and CHI3L1 in plasma improves accuracy of pancreatic cancer diagnosis. A panel assaying CEA and CA125 in plasma can predict survival for this clinical cohort of pancreatic cancer patients.
Chang
Stephanie T
ST
Department of Radiation Oncology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. stephanietchang@gmail.com
Zahn
Jacob M
JM
Horecka
Joe
J
Kunz
Pamela L
PL
Ford
James M
JM
Fisher
George A
GA
Le
Quynh T
QT
Chang
Daniel T
DT
Ji
Hanlee
H
Koong
Albert C
AC
D000465:Algorithms; D001681:Biological Assay / Q000379:methods* / Q000592:standards; D014408:Biomarkers, Tumor / Q000097:blood*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D016016:Proportional Hazards Models; D012044:Regression Analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor