A bile-based microRNA signature for differentiating malignant from benign pancreaticobiliary disease

Autor: Mireia Mato Prado, Jisce R. Puik, Leandro Castellano, Elena López-Jiménez, Daniel S. K. Liu, Laura L. Meijer, Tessa Y. S. Le Large, Eleanor Rees, Niccola Funel, Shivan Sivakumar, Stephen P. Pereira, Geert Kazemier, Babs M. Zonderhuis, Joris I. Erdmann, Rutger-Jan Swijnenburg, Andrea Frilling, Long R. Jiao, Justin Stebbing, Elisa Giovannetti, Jonathan Krell, Adam E. Frampton
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Experimental Hematology & Oncology, Vol 12, Iss 1, Pp 1-7 (2023)
Druh dokumentu: article
ISSN: 2162-3619
DOI: 10.1186/s40164-023-00458-3
Popis: Abstract Differentiating between pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) is crucial for the appropriate course of treatment, especially with advancements in the role of neoadjuvant chemotherapies for PDAC, compared to CCA. Furthermore, benign pancreaticobiliary diseases can mimic malignant disease, and indeterminate lesions may require repeated investigations to achieve a diagnosis. As bile flows in close proximity to these lesions, we aimed to establish a bile-based microRNA (miRNA) signature to discriminate between malignant and benign pancreaticobiliary diseases. We performed miRNA discovery by global profiling of 800 miRNAs using the NanoString nCounter platform in prospectively collected bile samples from malignant (n = 43) and benign (n = 14) pancreaticobiliary disease. Differentially expressed miRNAs were validated by RT-qPCR and further assessed in an independent validation cohort of bile from malignant (n = 37) and benign (n = 38) pancreaticobiliary disease. MiR-148a-3p was identified as a discriminatory marker that effectively distinguished malignant from benign pancreaticobiliary disease in the discovery cohort (AUC = 0.797 [95% CI 0.68–0.92]), the validation cohort (AUC = 0.772 [95% CI 0.66–0.88]), and in the combined cohorts (AUC = 0.752 [95% CI 0.67–0.84]). We also established a two-miRNA signature (miR-125b-5p and miR-194-5p) that distinguished PDAC from CCA (validation: AUC = 0.815 [95% CI 0.67–0.96]; and combined cohorts: AUC = 0.814 [95% CI 0.70–0.93]). Our research stands as the largest, multicentric, global profiling study of miRNAs in the bile from patients with pancreaticobiliary disease. We demonstrated their potential as clinically useful diagnostic tools for the detection and differentiation of malignant pancreaticobiliary disease. These bile miRNA biomarkers could be developed to complement current approaches for diagnosing pancreaticobiliary cancers. Graphical Abstract
Databáze: Directory of Open Access Journals
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