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

• Published in: Digestive diseases and sciences 2024-04, Vol.69 (4), p.1263-1273
• Main Authors: Huang, Jing, Gao, Ge, Ge, Yang, Liu, Jianzhou, Cui, Hongtu, Zheng, Ren, Wang, Jialin, Wang, Si, Go, Vay Liang, Hu, Shen, Liu, Yefu, Yang, Minwei, Sun, Yongwei, Shang, Dong, Tian, Yantao, Zhang, Zhigang, Xiang, Zhongyuan, Wang, Hongyang, Guo, Junchao, Xiao, Gary Guishan
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomarkers, Tumor; Cohort analysis; Cohort Studies; Early Detection of Cancer; Gastroenterology; Hepatology; Humans; Medical prognosis; Medicine; Medicine & Public Health; MicroRNAs; MicroRNAs - genetics; Oncology; Original Article; Pancreatic cancer; Pancreatic Neoplasms - pathology; Retrospective Studies; Transplant Surgery
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-024-08338-4

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. Graphical Abstract