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pmid:30560088
Up-Regulation of hsa-miR-210 Promotes Venous Metastasis and Predicts Poor Prognosis in Hepatocellular Carcinoma.
Jia Ji · Yuan Rong · Chang-Liang Luo · Shuo Li · Xiang Jiang · Hong Weng · Hao Chen · Wu-Wen Zhang · Wen Xie · Fu-Bing Wang
Frontiers in oncology · 2018 doi:10.3389/fonc.2018.00569
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Experiment
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Complete file
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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.", "claims": [{"id": "claim-method", "statement": "Kaplan-Meier survival analysis was conducted for univariate survival analysis, while Cox proportional hazards regression analysis was used for multivariate survival analysis (the analysis method is Forward:LR). The high throughput miRNA data of 375 HCC tissues and corresponding donors' information were downloaded from TCGA (https://cancergenome.nih.gov/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30560088", "locator": "sections[12] \"Statistical analysis\" paragraph 3", "quote": "Kaplan-Meier survival analysis was conducted for univariate survival analysis, while Cox proportional hazards regression analysis was used for multivariate survival analysis (the analysis method is Forward:LR)."}, {"asset": "source:pmid:30560088", "locator": "sections[5] \"Screening of prognostic miRNAs\" paragraph 2", "quote": "The high throughput miRNA data of 375 HCC tissues and corresponding donors' information were downloaded from TCGA (https://cancergenome.nih.gov/)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Primary data and platform annotation file of dataset GSE6857 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6857) were downloaded from GEO. The platform of this dataset is OSU-CCC MicroRNA Microarray Version 2.0 (GPL4700) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL4700). The dataset contains the expression profile of 230 miRNAs in 240 paired HCC tissues and adjacent non-tumor liver tissues, 1 lymph node tissue sample of an HCC patient and 1 normal liver tissue. In this study, we chose 180 HCC tissues without venous metastasis and 60 HCC tissues with venous metastasis to conduct the analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30560088", "locator": "sections[4] \"Screening of venous metastasis-related miRNAs\" paragraph 2", "quote": "Primary data and platform annotation file of dataset GSE6857 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6857) were downloaded from GEO. The platform of this dataset is OSU-CCC MicroRNA Microarray Version 2.0 (GPL4700) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL4700). The dataset contains the expression profile of 230 miRNAs in 240 paired HCC tissues and adjacent non-tumor liver tissues, 1 lymph node tissue sample of an HCC patient and 1 normal liver tissue. In this study, we chose 180 HCC tissues without venous metastasis and 60 HCC tissues with venous metastasis to conduct the analysis."}], "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:30560088"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE6857"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE6857"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30560088", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2018.00569", "sha256": "sha256:3cde0f2004c747839162823c13d1623eed766fe47dd1843dc227c2cb6b714d65", "bytes": 40937, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2018.00569", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6287006", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE6857", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6857", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE6857", "version": null, "note": "Primary data and platform annotation file of dataset GSE6857 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6857) were downloaded from GEO. 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