Development of a Serum-Based MicroRNA Signature for Early Detection of Pancreatic Cancer: A Multicenter Cohort Study

Dig Dis Sci. 2024 Apr;69(4):1263-1273. doi: 10.1007/s10620-024-08338-4. Epub 2024 Mar 7.

Abstract

Background: A grim prognosis of pancreatic cancer (PCa) was attributed to the difficulty in early diagnosis of the disease.

Aims: Identifying novel biomarkers for early detection of PCa is thus urgent to improve the overall survival rates of patients.

Methods: The study was performed firstly by identification of candidate microRNAs (miRNAs) in formalin-fixed, paraffin-embedded tissues using microarray profiles, and followed by validation in a serum-based cohort study to assess clinical utility of the candidates. In the cohorts, a total of 1273 participants from four centers were retrospectively recruited as two cohorts including training and validation cohort. The collected serum specimens were analyzed by real-time polymerase chain reaction.

Results: We identified 27 miRNAs expressed differentially in PCa tissues as compared to the benign. Of which, the top-four was selected as a panel whose diagnostic efficacy was fully assessed in the serum specimens. The panel exhibited superior to CA19-9, CA125, CEA and CA242 in discriminating patients with early stage PCa from healthy controls or non-PCa including chronic pancreatitis as well as pancreatic cystic neoplasms, with the area under the curves (AUC) of 0.971 (95% CI 0.956-0.987) and 0.924 (95% CI 0.899-0.949), respectively. Moreover, the panel eliminated interference from other digestive tumors with a specificity of 90.2%.

Conclusions: A panel of four serum miRNAs was developed showing remarkably discriminative ability of early stage PCa from either healthy controls or other pancreatic diseases, suggesting it may be developed as a novel, noninvasive approach for early screening of PCa in clinic.

Keywords: Circulating microRNA; Diagnosis; Noninvasive biomarker; Pancreatic cancer; Serum.

Publication types

  • Multicenter Study

MeSH terms

  • Biomarkers, Tumor
  • Cohort Studies
  • Early Detection of Cancer
  • Humans
  • MicroRNAs* / genetics
  • Pancreatic Neoplasms* / pathology
  • Retrospective Studies

Substances

  • MicroRNAs
  • Biomarkers, Tumor