SCIENCE@home

Improving a Plasma Biomarker Panel for Early Detection of Pancreatic Ductal Adenocarcinoma with Aminopeptidase N (ANPEP) and Polymeric Immunoglobin Receptor (PIGR).

Brianna M Krusen,P. Gimotty,Greg Donahue,Jacob E. Till,Melinda Yin,Erin E Carlson,W. Bamlet,Erica L. Carpenter,Shounak Majumder,Ann L. Oberg,Kenneth S. Zaret

Published 2026 in Clinical Cancer Research

ABSTRACT

PURPOSE Pancreatic ductal adenocarcinoma (PDAC) is typically detected too late for useful therapeutic interventions; hence, we sought blood biomarkers to detect early-stage disease. EXPERIMENTAL DESIGN Using mass spectrometry and ELISA on plasma pools from the University of Pennsylvania (Penn) and the Mayo Clinic (Mayo), we identified aminopeptidase N (ANPEP) and polymeric immunoglobulin receptor (PIGR) as increased in early-stage (stage I/II) PDAC plasma compared with controls. We tested ANPEP and PIGR, along with prior data for thrombospondin 2 (THBS2) and carbohydrate antigen 19-9 (CA19-9), in retrospective phase II studies using separate cohorts of PDAC plasmas at different stages versus healthy or nonmalignant disease controls (DC) from Penn (n = 135) and Mayo (n = 537). RESULTS Comparing healthy controls with stage I/II PDAC, we 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 Penn and 0.97 for Mayo. Notably, the four-marker panel elicited AUC of 0.87 for the Mayo stage I/II versus DC and 0.91 for stages I to IV versus DC. At a specificity of 95%, a plasma biomarker panel composed of 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 PDAC stages I to IV and 87.5% for PDAC stage I/II. CONCLUSIONS Adding ANPEP and PIGR to a plasma biomarker panel of CA19-9 and THBS2 enhances the detection of early-stage PDAC when comparing cancer versus healthy or nonmalignant DC. Given the concordance of our data in two retrospective phase II studies, assessments in prediagnostic cases are warranted.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-39 of 39 references · Page 1 of 1

CITED BY

  • No citing papers are available for this paper.

Showing 0-0 of 0 citing papers · Page 1 of 1