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pmid:31513595

Significantly different expression levels of microRNAs associated with vascular invasion in hepatocellular carcinoma and their prognostic significance after surgical resection.

Sung Kyu Song · Woon Yong Jung · Seung-Keun Park · Chul-Woon Chung · Yongkeun Park

PloS one · 2019 doi:10.1371/journal.pone.0216847

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title
Significantly different expression levels of microRNAs associated with vascular invasion in hepatocellular carcinoma and their prognostic significance after surgical resection.
doi
10.1371/journal.pone.0216847
pmid
31513595
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Sung Kyu Song
[1]
Woon Yong Jung
[2]
Seung-Keun Park
[3]
Chul-Woon Chung
[4]
Yongkeun Park
journal
PloS one
year
2019
abstract
BACKGROUND: Although gross vascular invasion (VI) has prognostic significance in patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection, few studies have investigated the relationship between gross VI and aberrant expression of microribonucleic acids (miRNAs and miRs). Thus, the objective of this study was to identify miRNAs selectively expressed in HCC with gross VI and investigate their prognostic significance. MATERIALS AND METHODS: Eligible two datasets (accession number: GSE20594 and GSE67140) were collected from the National Center for Biotechnology Information's (NCBI) Gene Expression Omnibus (GEO) database to compare miRNAs expression between HCC with and without gross VI. Differentially expressed miRNAs were externally validated using expression data from The Cancer Genome Atlas (TCGA) database. Prognostic significance and predicted functions of selected miRNAs for HCC were also investigated. RESULTS: Thirty-five miRNAs were differentially expressed between HCC with and without gross VI in both datasets. Among them, three miRNAs were validated using TCGA database. miR-99a, miR-100, and miR-148a were downregulated to a greater extent in patients with HCC and gross VI than in those with HCC but no gross VI. Receiver operating characteristic (ROC) curve analysis showed discriminatory power of these miRNAs in predicting gross VI. Multivariate survival analysis revealed that types of surgery, advanced tumor node metastasis (TNM) stage, and low expression of miR-100-5p were independently associated with tumor recurrence. It also revealed that types of surgery, advanced TNM stage, low expression of miR-100-5p and miR-148a-3p were independent risk factors for overall survival (OS) after hepatic resection for HCC. A text mining analysis revealed that these miRNAs were linked to multifaceted hallmarks of cancer, including "invasion and metastasis." CONCLUSIONS: Low expressions of miR-100-5p and miR-148a-3p were associated with gross VI and poor survival of patients after hepatic resection for HCC.
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To calculate hazard ratios (HRs) and 95% confidence intervals (CIs) and identify independent factors associated with RFS and OS, multivariate analysis was performed using Cox regression proportional hazards model.
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To calculate hazard ratios (HRs) and 95% confidence intervals (CIs) and identify independent factors associated with RFS and OS, multivariate analysis was performed using Cox regression proportional hazards model.
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High-throughput miRNA expression data were obtained from the National Center for Biotechnology Information’s (NCBI) Gene Expression Omnibus (GEO) dataset [15] (http://www.ncbi.nlm.nih.gov/geo/) under accession numbers GSE20594 and GSE67140, including miRNA expression profiles of HCC tumor samples and information about VI status.
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High-throughput miRNA expression data were obtained from the National Center for Biotechnology Information’s (NCBI) Gene Expression Omnibus (GEO) dataset [15] (http://www.ncbi.nlm.nih.gov/geo/) under accession numbers GSE20594 and GSE67140, including miRNA expression profiles of HCC tumor samples and information about VI status.
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Survival analysis
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Univariate analysis of factors predictive of recurrence-free survival and overall survival.
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To calculate hazard ratios (HRs) and 95% confidence intervals (CIs) and identify independent factors associated with RFS and OS, multivariate analysis was performed using Cox regression proportional hazards model.
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High-throughput miRNA expression data were obtained from the National Center for Biotechnology Information’s (NCBI) Gene Expression Omnibus (GEO) dataset [15] (http://www.ncbi.nlm.nih.gov/geo/) under accession numbers GSE20594 and GSE67140, including miRNA expression profiles of HCC tumor samples and information about VI status.
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To calculate hazard ratios (HRs) and 95% confidence intervals (CIs) and identify independent factors associated with RFS and OS, multivariate analysis was performed using Cox regression proportional hazards model.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31513595", "kind": "science-record", "revision": 7, "content_hash": "sha256:934949ff47d729a6d4a1629253ead08503b45e8053c06c68c8f3aba2b48812ce", "created_at": "2026-11-01T15:40:49Z", "updated_at": "2026-11-01T21:22:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Significantly different expression levels of microRNAs associated with vascular invasion in hepatocellular carcinoma and their prognostic significance after surgical resection.", "doi": "10.1371/journal.pone.0216847", "pmid": "31513595", "authors": ["Sung Kyu Song", "Woon Yong Jung", "Seung-Keun Park", "Chul-Woon Chung", "Yongkeun Park"], "journal": "PloS one", "year": 2019, "abstract": "BACKGROUND: Although gross vascular invasion (VI) has prognostic significance in patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection, few studies have investigated the relationship between gross VI and aberrant expression of microribonucleic acids (miRNAs and miRs). Thus, the objective of this study was to identify miRNAs selectively expressed in HCC with gross VI and investigate their prognostic significance.\nMATERIALS AND METHODS: Eligible two datasets (accession number: GSE20594 and GSE67140) were collected from the National Center for Biotechnology Information's (NCBI) Gene Expression Omnibus (GEO) database to compare miRNAs expression between HCC with and without gross VI. Differentially expressed miRNAs were externally validated using expression data from The Cancer Genome Atlas (TCGA) database. Prognostic significance and predicted functions of selected miRNAs for HCC were also investigated.\nRESULTS: Thirty-five miRNAs were differentially expressed between HCC with and without gross VI in both datasets. Among them, three miRNAs were validated using TCGA database. miR-99a, miR-100, and miR-148a were downregulated to a greater extent in patients with HCC and gross VI than in those with HCC but no gross VI. Receiver operating characteristic (ROC) curve analysis showed discriminatory power of these miRNAs in predicting gross VI. Multivariate survival analysis revealed that types of surgery, advanced tumor node metastasis (TNM) stage, and low expression of miR-100-5p were independently associated with tumor recurrence. It also revealed that types of surgery, advanced TNM stage, low expression of miR-100-5p and miR-148a-3p were independent risk factors for overall survival (OS) after hepatic resection for HCC. A text mining analysis revealed that these miRNAs were linked to multifaceted hallmarks of cancer, including \"invasion and metastasis.\"\nCONCLUSIONS: Low expressions of miR-100-5p and miR-148a-3p were associated with gross VI and poor survival of patients after hepatic resection for HCC.", "claims": [{"id": "claim-method", "statement": "To calculate hazard ratios (HRs) and 95% confidence intervals (CIs) and identify independent factors associated with RFS and OS, multivariate analysis was performed using Cox regression proportional hazards model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31513595", "locator": "sections[4] \"Survival analysis\" paragraph 2", "quote": "To calculate hazard ratios (HRs) and 95% confidence intervals (CIs) and identify independent factors associated with RFS and OS, multivariate analysis was performed using Cox regression proportional hazards model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "High-throughput miRNA expression data were obtained from the National Center for Biotechnology Information’s (NCBI) Gene Expression Omnibus (GEO) dataset [15] (http://www.ncbi.nlm.nih.gov/geo/) under accession numbers GSE20594 and GSE67140, including miRNA expression profiles of HCC tumor samples and information about VI status.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31513595", "locator": "sections[3] \"Study data and screening of differentially expressed miRNAs\" paragraph 2", "quote": "High-throughput miRNA expression data were obtained from the National Center for Biotechnology Information’s (NCBI) Gene Expression Omnibus (GEO) dataset [15] (http://www.ncbi.nlm.nih.gov/geo/) under accession numbers GSE20594 and GSE67140, including miRNA expression profiles of HCC tumor samples and information about VI status."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:31513595"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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