Development and Multiple Validation of the Protein Multi-marker Panel for Diagnosis of Pancreatic Cancer

Clin Cancer Res. 2021 Apr 15;27(8):2236-2245. doi: 10.1158/1078-0432.CCR-20-3929. Epub 2021 Jan 27.

Abstract

Purpose: To develop and validate a protein-based, multi-marker panel that provides superior pancreatic ductal adenocarcinoma (PDAC) detection abilities with sufficient diagnostic performance.

Experimental design: A total of 959 plasma samples from patients at multiple medical centers were used. To construct an optimal, diagnostic, multi-marker panel, we applied data preprocessing procedure to biomarker candidates. The multi-marker panel was developed using a training set comprised of 261 PDAC cases and 290 controls. Subsequent evaluations were performed in a validation set comprised of 65 PDAC cases and 72 controls. Further validation was performed in an independent set comprised of 75 PDAC cases and 47 controls.

Results: A multi-marker panel containing 14 proteins was developed. The multi-marker panel achieved AUCs of 0.977 and 0.953 for the training set and validation set, respectively. In an independent validation set, the multi-marker panel yielded an AUC of 0.928. The diagnostic performance of the multi-marker panel showed significant improvements compared with carbohydrate antigen (CA) 19-9 alone (training set AUC = 0.977 vs. 0.872, P < 0.001; validation set AUC = 0.953 vs. 0.832, P < 0.01; independent validation set AUC = 0.928 vs. 0.771, P < 0.001). When the multi-marker panel and CA 19-9 were combined, the diagnostic performance of the combined panel was improved for all sets.

Conclusions: This multi-marker panel and the combined panel showed statistically significant improvements in diagnostic performance compared with CA 19-9 alone and has the potential to complement CA 19-9 as a diagnostic marker in clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Pancreatic Ductal / diagnosis*
  • Carcinoma, Pancreatic Ductal / pathology
  • Case-Control Studies
  • Datasets as Topic
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / pathology
  • Proteomics
  • ROC Curve

Substances

  • Biomarkers, Tumor