Dataset Information

Joint Covariate Detection on Expression Profiles for Identifying MicroRNAs Related to Venous Metastasis in Hepatocellular Carcinoma.

ABSTRACT: Expression profiles of cancer are generally composed of three dimensions including gene probes, patients (e.g., metastasis or non-metastasis) and tissues (i.e., cancer or normal cells of a patient). In order to combine these three dimensions, we proposed a joint covariate detection that not only considered projections on gene probes and tissues simultaneously, but also concentrated on distinguishing patients into different groups. Due to highly lethal malignancy of hepatocellular carcinoma, we chose data GSE6857 to testify the effectiveness of our method. A bootstrap and accumulation strategy was introduced in, which could select candidate microRNAs to distinguish metastasis from non-metastasis patient group. Two pairs of microRNAs were further selected. Each component of either significant microRNA pair was derived from different cliques. Targets were sought and pathway analysis were made, which might reveal the mechanism of venous metastasis in primary hepatocellular carcinoma.

SUBMITTER: Zhao X

PROVIDER: S-EPMC5509738 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Joint Covariate Detection on Expression Profiles for Identifying MicroRNAs Related to Venous Metastasis in Hepatocellular Carcinoma.

Zhao Xudong X Wang Lei L Chen Guangsheng G

Scientific reports 20170713 1

Expression profiles of cancer are generally composed of three dimensions including gene probes, patients (e.g., metastasis or non-metastasis) and tissues (i.e., cancer or normal cells of a patient). In order to combine these three dimensions, we proposed a joint covariate detection that not only considered projections on gene probes and tissues simultaneously, but also concentrated on distinguishing patients into different groups. Due to highly lethal malignancy of hepatocellular carcinoma, we c ...[more]

PMID: 28706271

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Project description:Objective: To investigate the potential biomarkers for venous metastasis of hepatocellular carcinoma (HCC), and briefly discuss their target genes and the signaling pathways they are involved in. Materials and Method: The dataset GSE6857 was downloaded from GEO. Significantly differentially expressed miRNAs were identified using the R package "limma," After that, the survival analysis was conducted to discover the significance of these up-regulated miRNAs for the prognosis of HCC patients. Additionally, miRNAs which were up-regulated in venous metastasis positive HCC tissues and were significant for the prognosis of HCC patients were further verified in clinical samples using RT-qPCR. The miRNAs were then analyzed for their correlations with clinical characteristics including survival time, AFP level, pathological grade, TNM stage, tumor stage, lymph-node metastasis, distant metastasis, child-pugh score, vascular invasion, liver fibrosis and race using 375 HCC samples downloaded from the TCGA database. The target genes of these miRNAs were obtained using a miRNA target gene prediction database, and their functions were analyzed using the online tool DAVID. Results: 15 miRNAs were differentially expressed in samples with venous metastasis, among which 7 were up-regulated in venous metastasis positive HCC samples. As one of the up-regulated miRNAs, hsa-miR-210 was identified as an independent prognostic factor for HCC. Using RT-qPCR, it was evident that hsa-miR-210 expression was significantly higher in venous metastasis positive HCC samples (p = 0.0036). Further analysis indicated that hsa-miR-210 was positively associated with AFP level, pathological grade, TNM stage, tumor stage and vascular invasion. A total of 168 hsa-miR-210 target genes, which are mainly related to tumor metastasis and tumor signaling pathways, were also predicted in this study. Conclusion: hsa-miR-210 might promote vascular invasion of HCC cells and could be used as a prognostic biomarker.

Project description:BackgroundHepatocellular carcinoma (HCC) is one of the most lethal cancer, mainly attributing to its high tendency to metastasis. Vascular invasion provides a direct path for solid tumor metastasis. Mounting evidence has demonstrated that microRNAs (miRNAs) are related to human cancer onset and progression including invasion and metastasis.MethodsIn search of invasion-metastasis-associated miRNAs in HCC, microarray dataset GSE67140 was downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) were obtained by R software package and the potential target genes were predicted by miRTarBase. The database for annotation, visualization and integrated discovery (DAVID) was introduced to perform functional annotation and pathway enrichment analysis for these potential targets of DE-miRNAs. Protein-protein interaction (PPI) network was established by STRING database and visualized by Cytoscape software. The effects of the miR-494-3p and miR-126-3p on migration and invasion of HCC cell lines were evaluated by conducting wound healing assay and transwell assay.ResultsA total of 138 DE-miRNAs were screened out, including 57 upregulated miRNAs and 81 downregulated miRNAs in human HCC tumors with vascular invasion compared with human HCC tumors without vascular invasion. 762 target genes of the top three upregulated and downregulated miRNAs were predicted, and they were involved in HCC-related pathways, such as pathway in cancer, focal adhesion and MAPK signaling pathway. In the PPI network, the top 10 hub nodes with higher degrees were identified as hub genes, such as TP53 and MYC. Through constructing the miRNA-hub gene network, we found that most of hub genes could be potentially modulated by miR-494-3p and miR-126-3p. Of note, miR-494-3p and miR-126-3p was markedly upregulated and downregulated in HCC cell lines and tissues, respectively. In addition, overexpression of miR-494-3p could significantly promote HCC migration and invasion whereas overexpression of miR-126-3p exerted an opposite effect.ConclusionsTargeting miR-494-3p and miR-126-3p may provide effective and promising approaches to suppress invasion and metastasis of HCC.

Dataset Information

Joint Covariate Detection on Expression Profiles for Identifying MicroRNAs Related to Venous Metastasis in Hepatocellular Carcinoma.

Publications

Joint Covariate Detection on Expression Profiles for Identifying MicroRNAs Related to Venous Metastasis in Hepatocellular Carcinoma.

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