| dc.description.abstract | Background: Intrahepatic cholangiocarcinoma (iCCA) is the second most common
liver malignancy with two main divisions, large-duct and small-duct iCCA, according to
the World Health Organization. Unlike large-duct iCCA, there is currently a few studies
working on the origin of small-duct type. Thus, the cells of small-duct iCCA origin
should be intensively explored to give evidence for further research on its early
diagnosis and disease treatment.
Methods: In this study, we used the raw data, fastq files, generated by droplet-based
single-cell RNA sequencing 10X Genomics from small-duct iCCA (recognized by HE
staining) on public database for analysis. Then, the bioinformatics tools (Cellranger
and Seurat) were applied for data preprocessing and Malignant cells separation. From
the gene expression and copy number variations (CNVs) profiles (detected from gene
expression data by CopyKAT) of Malignant cells, trajectories were built by Slingshot.
From the constructed trajectories, the GSEA software was employed to trace the origin.
Results: First, dataset of 28559 single cells from 5 iCCA samples of 5 patients were
collected to process in which 7800 cells were small-duct iCCA malignancy. Second, the
bioinformatics pipeline for analyzing 10X Genomics data was constructed by
integrating the tools and packages mentioned in Methods part. Besides, the pipeline
was automatically processed (by Snakemake tool) for data investigation. From the
pipeline result, the trajectories constructed from gene expression profile were partially
consistent with the ones constructed from CNVs, and they were all used for reflecting
the cancerous differentiation. Third, after analyzing the gene set enrichment between
start site and end site of trajectories, the cells of origin for small-duct iCCA were
indicated.
Conclusion: The result of algorithm suggests that Hepatoblasts and Hepatocytes could
be the origin of small-duct iCCA. | en_US |
