Circulating microRNA-21 as a prognostic, biological marker in cholangiocarcinoma

The prognosis of cholangiocarcinoma (CCA) is generally poor because there is a lack of effective diagnostic tools including laboratory assessments and imageological examination. Therefore, a novel biological marker (biomarker) to effectively diagnose cancer is highly desirable in clinical. Previously, serum microRNAs as biomarkers of cancers have been reported. However, it was still unclear about the clinical significance of serum microRNA-21 (miR-21) expression levels for CCA.

The serum samples were separately collected from fifty patients of CCA, 15 patients of hepatolithiasis, and 15 healthy volunteers; quantitative real-time polymerase chain reaction was used for measuring miR-21 expression level in serum. The clinicopathological data were recorded before patients discharged.

In the CCA serum, the expression level of miR-21 significantly upregulated (P < 0.05). With the tumor, node, and metastasis stage developed (Stage I vs. III and IV, P < 0.05), the serum miR-21 expression level increased, but there was no statistical difference between Stage I patients and hepatolithiasis patients or healthy control (P > 0.05 for both). Furthermore, the miR-21 level was significant difference between pre- and post-operative serum (P < 0.05) for the high miR-21 expression group. The serum miR-21 expression levels were defective in discriminating patients with CCA from healthy control subjects by receiver-operator curve analysis because the area under the curve (AUC) value was 0.871 which was not better than the conventional CCA markers-carbohydrate antigen 19-9 (AUC value = 0.96). However, in serum, high expression level miR-21 was significantly related to clinical stage, invasion depth, lymph vessel infiltration, metastasis status, differentiation status, whether to resection, and poor survival of CCA patients (P < 0.05 for all).

This study suggested that serum miR-21 was a promising biomarker for diagnosing the late stage CCA and would have potential to be a useful prognostic biomarker of CCA.