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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
Identification of biomarkers of intrahepatic cholangiocarcinoma via integrated analysis of mRNA and miRNA microarray
Yaqing Chen1, Dan Liu2, Pengfei Liu3
1Department of VIP Ward, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China.
Abstract:
The present study aimed to identify potential therapeutic targets of intrahepatic cholangiocarcinoma (ICC) via integrated analysis of gene (transcript version) and microRNA (miRNA/miR) expression. The miRNA microarray dataset GSE32957 contained miRNA expression data from 16 ICC, 7 mixed type of combined hepatocellular‑cholangiocarcinoma (CHC), 2 hepatic adenoma, 3 focal nodular hyperplasia (FNH) and 5 healthy liver tissue samples, and 2 cholangiocarcinoma cell lines. In addition, the mRNA microarray dataset GSE32879 contained mRNA expression data from 16 ICC, 7 CHC, 2 hepatic adenoma, 5 FNH and 7 healthy liver tissue samples. The datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and miRNAs (DEMs) in ICC samples compared with healthy liver tissues were identified via the limma package, following data preprocessing. Genes that exhibited alternative splicing (AS) in ICC samples were identified via AltAnalyze software. Functional enrichment analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Analysis. Target genes of DEMs were identified using the TargetScan database. The regulatory association between DEMs and any overlaps among DEGs, alternative splicing genes (ASGs) and target genes of DEMs were retrieved, and a network was visualized using the Cytoscape software. A total of 2,327 DEGs, 70 DEMs and 623 ASGs were obtained. Functional enrichment analysis indicated that DEGs were primarily enriched in biological processes and pathways associated with cell activity or the immune system. A total of 63 overlaps were obtained among DEGs, ASGs and target genes of DEMs, and a regulation network that contained 243 miRNA‑gene regulation pairs was constructed between these overlaps and DEMs. The overlapped genes, including sprouty‑related EVH1 domain containing 1, protein phosphate 1 regulatory subunit 12A, chromosome 20 open reading frame 194, and DEMs, including hsa‑miR‑96, hsa‑miR‑1 and hsa‑miR‑25, may be potential therapeutic targets for the future treatment of ICC.
Insights
This study identified potential therapeutic targets for intrahepatic cholangiocarcinoma (ICC) by analyzing gene and microRNA expression. Key genes and microRNAs were pinpointed, offering new avenues for ICC treatment strategies.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Intrahepatic cholangiocarcinoma (ICC) is a challenging cancer with limited therapeutic options.
- Identifying novel therapeutic targets is crucial for improving patient outcomes.
Purpose of the Study:
- To identify potential therapeutic targets for ICC through integrated analysis of gene and microRNA expression.
- To explore differentially expressed genes (DEGs), microRNAs (DEMs), and alternatively spliced genes (ASGs) in ICC.
- To construct a regulatory network of miRNA-gene interactions relevant to ICC.
Main Methods:
- Utilized gene expression dataset GSE32879 and microRNA expression dataset GSE32957 from the Gene Expression Omnibus database.
- Identified DEGs and DEMs using the limma package and ASGs using AltAnalyze software.
- Performed functional enrichment analysis and constructed a regulatory network using Cytoscape software.
Main Results:
- Identified 2,327 DEGs, 70 DEMs, and 623 ASGs in ICC samples compared to healthy liver tissues.
- Functional enrichment analysis revealed DEGs are involved in cell activity and immune system processes.
- Constructed a regulatory network with 243 miRNA-gene pairs, highlighting 63 key overlaps.
Conclusions:
- Several genes (e.g., sprouty-related EVH1 domain containing 1) and microRNAs (e.g., hsa-miR-96) were identified as potential therapeutic targets for ICC.
- The integrated analysis provides a foundation for developing targeted therapies against ICC.
- Further research into these identified targets could lead to novel treatment strategies for intrahepatic cholangiocarcinoma.
