Circulating microRNAs Expression as Prognosis Biomarker of Cholangiocarcinoma

Cholangiocarcinoma (CCA) is a significant problem in Southeast Asia, particularly Thailand. Changes in the expression of microRNAs (miRNA), is one of the mechanisms associated with the pathogenesis and progression of cancer.

In the present study, serum miRNA expression from advanced-stage intrahepatic CCA patients was investigated using the high-throughput technique (Nanostring Ncounter© technology).

Twenty-four intrahepatic CCA patients and eight healthy subjects were enrolled in this study. The CCA group was subgrouped according to disease progression into non-metastatic CCA and metastatic CCA.

Of the 803 miRNAs, expression of 239 miRNAs was significantly different among the three groups (p < 0.001). Among them, miR-302d-3p showed the most significant expression (p < 9.02x10-7, FDR: 7.25x10-4), with upregulation in patients with metastatic CCA compared to non-metastic CCA and healthy groups. Fold change analysis revealed that miR-320e expression was the most significantly upregulated across all three groups (p < 0.001). Additionally, the expression levels of miR-223-3p, miR-23a-3p, and miR-302d-3p were significantly increased in patients with both metastatic and non-metastatic CCA compared to healthy controls. Several miRNAs were significantly downregulated, among them, miR-16-5p and miR-451a showed significant downregulation in metastatic and non-metastatic CCA compared with healthy groups.

These findings indicate that a panel of circulating miRNAs may serve as a useful tool for the diagnosis and prognosis of intrahepatic cholangiocarcinoma, warranting further validation in larger cohorts. Additionally, the accuracy of diagnostic tests may be improved by increasing the sample size and including diverse clinical subgroups to enhance the robustness and generalizability of the results.