Bile-derived circulating extracellular miR-30d-5p and miR-92a-3p as potential biomarkers for cholangiocarcinoma

Hye Sook Han; Mi Jin Kim; Joung-Ho Han; Jieun Yun; Hee Kyung Kim; Yaewon Yang; Ki Bae Kim; Seon Mee Park

doi:10.1016/j.hbpd.2019.10.009

Bile-derived circulating extracellular miR-30d-5p and miR-92a-3p as potential biomarkers for cholangiocarcinoma

Hepatobiliary Pancreat Dis Int. 2020 Feb;19(1):41-50. doi: 10.1016/j.hbpd.2019.10.009. Epub 2019 Nov 8.

Authors

Hye Sook Han¹, Mi Jin Kim², Joung-Ho Han³, Jieun Yun⁴, Hee Kyung Kim¹, Yaewon Yang², Ki Bae Kim², Seon Mee Park¹

Affiliations

¹ Department of Internal Medicine, Chungbuk National University Hospital, Cheongju 28644, Korea; Departments of Internal Medicine, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
² Department of Internal Medicine, Chungbuk National University Hospital, Cheongju 28644, Korea.
³ Department of Internal Medicine, Chungbuk National University Hospital, Cheongju 28644, Korea; Departments of Internal Medicine, Chungbuk National University College of Medicine, Cheongju 28644, Korea. Electronic address: joungho@cbnu.ac.kr.
⁴ Department of Pharmaceutical Engineering, College of Science Engineering, Cheongju University, Cheongju 28644, Korea.

PMID: 31784323
DOI: 10.1016/j.hbpd.2019.10.009

Abstract

Background: Cholangiocarcinoma (CCA) is from cholangiocytes, and therefore bile is a potentially rich source of biomarkers for CCA. The aim of the study was to identify and validate microRNAs (miRNAs) in bile samples that are differentially expressed between benign biliary disease (BBD) and CCA.

Methods: Bile samples from 106 patients with obstructive biliary disease were allocated consecutively to a discovery set (10 patients with BBD and 11 with CCA) and then a validation set (48 patients with BBD and 37 with CCA). An miRNA microarray platform was used to screen 1209 miRNAs in the discovery set. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the profiling results in the discovery and validation sets. In addition, the levels of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were determined from patient serum samples.

Results: Microarray profiling showed that miR-30d-5p and miR-92a-3p were significantly upregulated in bile from the CCA group compared with those from the BBD group. qRT-PCR results indicated that the expression levels of miR-30d-5p and of miR-92a-3p were significantly upregulated in the CCA group compared to the BBD group, validating the miRNA microarray results. Pathway analysis suggested that putative target genes of miR-30d-5p and of miR-92a-3p were involved in CCA-associated signalling pathways, such as Hippo, Wnt, p53, MAPK, and EGFR. Receiver operating curve analysis revealed that the areas under the curve for bile miR-30d-5p, miR-92a-3p, serum CA19-9, and CEA were 0.730, 0.652, 0.675, and 0.603, respectively, and bile miR-30d-5p showed the best diagnostic performance with a sensitivity of 81.1% and a specificity of 60.5%.

Conclusions: The levels of extracellular miR-30d-5p and miR-92a-3p in bile were significantly higher in patients with CCA than those in patients with BBD. Bile-derived circulating extracellular miR-30d-5p and miR-92a-3p are potential biomarkers for discriminating CCA from BBD.

Keywords: Bile; Biomarkers; Cholangiocarcinoma; MicroRNA.

MeSH terms

Adult
Aged
Bile / chemistry*
Bile Duct Neoplasms / diagnosis*
Biomarkers, Tumor / analysis
Cholangiocarcinoma / diagnosis*
Female
Humans
Male
MicroRNAs / analysis*
Middle Aged
Real-Time Polymerase Chain Reaction

Substances

Biomarkers, Tumor
MIRN30b microRNA, human
MIRN92 microRNA, human
MicroRNAs