Document Type

Journal Article

Publication Date

4-23-2015

Journal

BMC Cancer

Volume

Volume 15

Issue

1

Inclusive Pages

Article number 309

DOI

10.1186/s12885-015-1270-5

Abstract

Background

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive tumor of the bile duct, and a significant public health problem in East Asia, where it is associated with infection by the parasiteOpisthorchis viverrini. ICC is often detected at an advanced stage and with a poor prognosis, making a biomarker for early detection a priority.

Methods

We have comprehensively profiled miRNA expression levels in ICC tumor tissue using small RNA-Seq and validated these profiles using quantitative PCR on matched plasma samples.

Results

Distinct miRNA profiles were associated with increasing histological differentiation of ICC tumor tissue. We also observed that histologically normal tissue adjacent to ICC tumor displayed miRNA expression profiles more similar to tumor than liver tissue from healthy donors. In plasma samples, an eight-miRNA signature associated with ICC, regardless of the degree of histological differentiation of its matched tissue, forming the basis of a circulating miRNA-based biomarker for ICC.

Conclusions

The association of unique miRNA profiles with different ICC subtypes suggests the involvement of specific miRNAs during ICC tumor progression. In plasma, an eight-miRNA signature associated with ICC could form the foundation of an accessible (plasma-based) miRNA-based biomarker for the early detection of ICC.

Comments

Reproduced with permission of BioMed Central. BMC Cancer.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Peer Reviewed

1

Open Access

1

Additional Files
qPCR Plate Layout..xlsx (11 kB)
qPCR Plate Layout.
EdgeR output from miRNA differential expression analysis.xlsx (47 kB)
EdgeR output from miRNA differential expression analysis
Regression analysis comparing fold change.pdf (106 kB)
Regression analysis comparing fold change (FC) values from miRNAs identified as significantly dysregulated in microarray analysis to FC values from RNA-Seq analysis of the same tissue. When all samples where compared to their matched D-NT tissue FC values were strongly correlated (Pearson’s correlation of 0.94; PC on graph). Similarly, when analyses were broken into comparisons between samples of the same histological grade, strong correlation was observed in the FC values obtained using both methods.
Summary of miRNA expression in plasma as measured using custom-made qPCR plate.xlsx (10 kB)
Summary of miRNA expression in plasma as measured using custom-made qPCR plate
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