Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis

Adv Sci (Weinh). 2024 Mar;11(11):e2306373. doi: 10.1002/advs.202306373. Epub 2024 Jan 10.

Abstract

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

Keywords: Glypican 1 mRNA in exosomes and protein in tumor-associated microvesicles as a dual biomarker; PDAC screening and chemotherapy prognosis; immune lipoplex nanoparticle biochip assay; single extracellular vesicle analysis.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Pancreatic Ductal* / diagnosis
  • Carcinoma, Pancreatic Ductal* / genetics
  • Extracellular Vesicles* / metabolism
  • Glypicans / genetics
  • Glypicans / metabolism
  • Humans
  • Pancreatic Neoplasms* / diagnosis
  • Pancreatic Neoplasms* / genetics
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Biomarkers, Tumor
  • Glypicans
  • RNA, Messenger
  • GPC1 protein, human