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pmid:30311168
Novel MicroRNA-Based Risk Score Identified by Integrated Analyses to Predict Metastasis and Poor Prognosis in Breast Cancer.
Tstutomu Kawaguchi · Li Yan · Qianya Qi · Xuan Peng · Stephen B Edge · Jessica Young · Song Yao · Song Liu · Eigo Otsuji · Kazuaki Takabe
Annals of surgical oncology · 2018 doi:10.1245/s10434-018-6859-x
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Experiment
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Complete file
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MicroRNAs (miRNAs) are known to play major roles in cancer biology including metastasis. This study aimed to develop a novel miRNA risk score to predict patient survival and metastasis in breast cancer.\nMETHODS: An integrated unbiased approach was applied to derive a composite risk score for prognosis based on miRNA expression in primary breast tumors in 1051 breast cancer patients from The Cancer Genome Atlas (TCGA). Further analysis of the risk score with metastasis/recurrence was performed using the TCGA data set and validated in a separate patient population using small RNA sequencing.\nRESULTS: The three-miRNAs risk score (miR-19a, miR-93, and miR-106a) was developed using the TCGA cohort, which predicted poor prognosis (p = 0.0005) independently of known clinical risk factors. The prognostic value was validated in another three following independent cohorts: GSE19536 (p = 0.0009), GSE22220 (p = 0.0003), and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (p = 0.0023). The three-miRNAs risk score predicted bone recurrence in TCGA (p = 0.0052), and the findings were validated in another independent population of patients who experienced bone recurrence and age/stage-matched patients without any recurrence. The three-miRNAs risk score enriched multiple metastasis-related gene sets such as angiogenesis and epithelial mesenchymal transition in a gene-set-enrichment analysis.\nCONCLUSIONS: The authors developed the novel miRNA-based risk score, which is a promising biomarker for prediction of worse survival and bone recurrence potential in breast cancer.", "claims": [{"id": "claim-method", "statement": "To compare the survival curves between subgroups groups, the Kaplan-Meier method with log-rank test was used. As we previously reported, Cox proportional hazard models were used for multivariable analysis to derive hazard ratios (HR) and 95% confidence intervals (CI), and the proportional hazard assumption was tested using Schoenfeld residuals25–27,29–31. Cumulative Incidence Functions (CIFs) were estimated to assess the probability of metastatic to different sites, and tested for statistically significant in TCGA cohort. Gene Set Enrichment Analysis (GSEA) was performed using software provided by the Broad Institute (http://software.broadinstitute.org/gsea/index.jsp)32.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30311168", "locator": "sections[7] \"Statistical analysis\" paragraph 2", "quote": "To compare the survival curves between subgroups groups, the Kaplan-Meier method with log-rank test was used. As we previously reported, Cox proportional hazard models were used for multivariable analysis to derive hazard ratios (HR) and 95% confidence intervals (CI), and the proportional hazard assumption was tested using Schoenfeld residuals25–27,29–31. Cumulative Incidence Functions (CIFs) were estimated to assess the probability of metastatic to different sites, and tested for statistically significant in TCGA cohort. Gene Set Enrichment Analysis (GSEA) was performed using software provided by the Broad Institute (http://software.broadinstitute.org/gsea/index.jsp)32."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during the current study are available from the corresponding author on reasonable request", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30311168", "locator": "sections[17] \"fn-group\" paragraph 1", "quote": "The datasets generated during the current study are available from the corresponding author on reasonable request"}], "state": "complete"}, {"id": "claim-target-result", "statement": "The three-miRNA signature score (miR-19a, miR-93, and miR-106a) predicted poor prognosis in TCGA and was validated in three independent cohorts.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:30311168", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The three-miRNA signature score (miR-19a, miR-93, and miR-106a) was developed using the TCGA cohort that predicted poor prognosis (p=0.0005), independent of known clinical risk factors. The prognostic value was validated in another three independent cohorts (GSE19536, p=0.0009; GSE22220, p=0.0003; and METABRIC, p=0.0023, respectively)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The three-miRNA signature score (miR-19a, miR-93, and miR-106a) predicted poor prognosis in TCGA and was validated in three independent cohorts.", "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:30311168"], "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:GSE19536"], "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:GSE19536"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30311168", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1245/s10434-018-6859-x", "sha256": 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