Scientific Update: Bile MicroRNA Profiling May Facilitate Cholangiocarcinoma Diagnosis

In diagnosing cholangiocarcinoma, it is essential to distinguish it from other conditions that can have similar presentation, such as pancreatic ductal adenocarcinoma and benign liver/bile duct tumors. A recent study thus investigated whether profiling microRNA (miRNA) molecules in bile could help identify cholangiocarcinoma. Bile runs close to and often in contact with pancreaticobiliary lesions, so the researchers hypothesized that there would be differences in the bile miRNA profiles across conditions.

The study first examined bile samples from a "discovery cohort," which included 57 patients with a mix of benign and malignant conditions: 14 benign, six cholangiocarcinoma (CCA), three ampullary carcinomas, and 28 pancreatic ductal adenocarcinomas (PDAC). Global miRNA expression profiling revealed possible dysregulation of multiple miRNAs in malignant pancreaticobiliary conditions. RT-qPCR (another gene expression analysis technique) was used for validation and confirmed dysregulation of the miRNA miR-148a-3p. Additional analysis in an independent cohort of 75 patients and the combined group showed similar results, suggesting that miR-148a-3p could be used as a biomarker for malignancy during diagnosis.

While miR-148a-3p may aid in distinguishing benign vs. malignant pancreaticobiliary conditions, additional biomarkers are needed to identify specific cancer types. In the discovery cohort, the researchers noted differential expression levels of several miRNAs in CCA vs. PDAC: miR-125b-5p and miR-194-5p were more abundant in PDAC compared to CCA, while miR-451a levels were lower in PDAC. A similar analysis in the validation and combined cohorts confirmed elevation of miR-125b-5p and miR-194-5p in PDAC vs. CCA. These two miRNAs thus merit further investigation as biomarkers that could distinguish PDAC from CCA during diagnosis, which can have important implications for treatment planning. Additional studies should include early-stage tumor samples to test whether miRNA profiling could improve early detection of cholangiocarcinoma and other pancreaticobiliary cancers.

Mato Prado et al. Experimental Hematology & Oncology (2023) 12:101

Kelly Butler

Kelly Butler
Yale School of Medicine, MD program student