Pancreatic ductal adenocarcinoma is the most common form of pancreatic cancer, and is most often diagnosed at advanced, unresectable stages, when 5-year survival is just 3%.
The results from two retrospective phase II studies investigating blood biomarkers to detect early-stage pancreatic ductal adenocarcinoma has found that adding aminopeptidase N (ANPEP) and polymeric immunoglobulin receptor (PIGR) to a plasma blood panel of carbohydrate antigen 19-9 (CA19-9) and thrombospondin-2 (THBS2) enhanced the detection of early-stage pancreatic ductal adenocarcinoma compared with measuring CA19-9 levels alone. The study by Krusen et al is published in Clinical Cancer Research.
Study Methodology
To identify novel biomarkers of pancreatic cancer, the researchers analyzed plasma samples from two cohorts, including 537 samples from the Mayo Clinic (Mayo) and 135 from the Hospital of the University of Pennsylvania (Penn). The cohorts comprised patients with confirmed pancreatic cancer, healthy individuals, and patients with benign pancreatic disease.
The investigators used mass spectrometry and ELISA on plasma pools from Mayo and Penn to compare protein levels across the plasma samples and identified ANPEP and PIGR as increased in early-stage pancreatic ductal adenocarcinoma plasma compared with the controls. They then developed a panel that measured the blood levels of four biomarkers, including ANPET and PIGR, together with CA19-9 and THBS2.
Results
When comparing the healthy controls with stage I/II pancreatic ductal adenocarcinoma, the researchers obtained area under the receiver-operating characteristic curves (AUC) of 0.78 (95% confidence interval [CI] = 0.68–0.86)/0.80 (95% CI = 0.74–0.85; ANPEP) and 0.81 (95% CI = 0.70–0.88)/0.86 (95% CI = 0.82–0.90; PIGR) for the Penn/Mayo phase II studies, respectively.
In multivariable models, CA19-9/THBS2/ANPEP, CA19-9/THBS2/PIGR, and CA19-9/THBS2/ANPEP/PIGR elicited AUC of 0.94 to 0.96 for the Penn and 0.97 for Mayo cohorts. Notably, the four-marker panel elicited AUC of 0.87 for the Mayo stage I to II vs disease control and 0.91 for stage I to IV vs disease control. At a specificity of 95%, a plasma biomarker panel comprising CA19-9 (≥ 35 U/mL), THBS2 (≥ 42 ng/mL), ANPEP (≥ 2,995 ng/mL), and PIGR (≥ 1,800 ng/mL) yielded a sensitivity of 91.9% for stage I to IV pancreatic ductal adenocarcinoma and 87.5% for stage I to II pancreatic ductal adenocarcinoma.
“Adding ANPEP and PIGR to a plasma biomarker panel of CA19-9 and THBS2 enhances the detection of early-stage [pancreatic ductal adenocarcinoma] when comparing cancer vs healthy or nonmalignant [disease controls]. Given the concordance of our data in two retrospective phase II studies, assessments in pre-diagnostic cases are warranted,” concluded the study authors.
Clinical Significance
“With the addition of ANPEP and PIGR, the panel helps to overcome known limitations associated with CA19-9 and THBS2 testing, such as patients who genetically underexpress CA19-9 or tumors that present as different molecular subtypes, and could, therefore, reduce the number of missed cancer cases while keeping false positives low,” said Kenneth S. Zaret, PhD, Professor, Perelman School of Medicine at the University of Pennsylvania, and lead author of this study, in a statement.
Dr. Zaret is the corresponding author of this study.
DISCLOSURE: For full disclosures of the study authors, visit aacrjournals.org/clincancerres.
