Combined Exosomal GPC1, CD82, and Serum CA19-9 as Multiplex Targets: A Specific, Sensitive, and Reproducible Detection Panel for the Diagnosis of Pancreatic Cancer

Mol Cancer Res. 2020 Feb;18(2):300-310. doi: 10.1158/1541-7786.MCR-19-0588. Epub 2019 Oct 29.

Abstract

Pancreatic cancer is a highly lethal malignancy with poor prognosis due to the lack of early symptoms and resultant late diagnosis. Thus, it is extremely urgent to establish a simple and effective method for the early diagnosis of pancreatic cancer. Although some studies have provided positive evidence for the use of exosomal surface protein glypican-1 (GPC1) as a biomarker for early screening, its clinical application is still controversial. Here, we systematically verified the role of exosomal GPC1 as a potential screening biomarker. First, bottleneck problems of a stable detection method and an identification standard were systematically studied, and a Python-based standardized data processing method was established to analyze exosomal GPC1 expression. Second, a detection panel consisting of exosomal GPC1, exosomal cluster of differentiation 82 (CD82), and serum carbohydrate antigen 19-9 (CA19-9) was employed for pancreatic cancer detection. This panel exhibited excellent diagnostic results (AUC = 0.942) and could effectively distinguish healthy people from patients with pancreatic cancer (P value threshold = 0.2282) and patients with pancreatitis from patients with pancreatic cancer (P value threshold = 0.5467). IMPLICATIONS: These results indicate that the combined detection of exosomal GPC1, exosomal CD82, and serum CA19-9 shows great promise as a standard method for pancreatic cancer detection and that this panel could be further applied for screening pancreatic cancer in Chinese populations.

Publication types

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

MeSH terms

  • Biomarkers, Tumor / blood
  • CA-19-9 Antigen / blood*
  • Cell Differentiation / physiology
  • Exosomes / metabolism*
  • Female
  • Glypicans / metabolism*
  • Humans
  • Kangai-1 Protein / metabolism*
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / pathology
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • CA-19-9 Antigen
  • CD82 protein, human
  • GPC1 protein, human
  • Glypicans
  • Kangai-1 Protein