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pmid:33879671
In silico screening using bulk and single-cell RNA-seq data identifies RIMS2 as a prognostic marker in basal-like breast cancer: A retrospective study.
Lingyun Zhang · Zheng Liu · Jingqiang Zhu
Medicine · 2021 doi:10.1097/MD.0000000000025414
Paper
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Experiment
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Analysis
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Complete file
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This study tried to screen prognosis-related genes in basal-like breast tumors and evaluate their correlations with cellular states at the single-cell level.Bulk RNA-seq data of basal-like tumor cases from The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) and single-cell RNA-seq from GSE75688 were retrospectively reviewed. Kaplan-Meier survival curves, univariate and multivariate analysis based on Cox regression model were conducted for survival analysis. Gene set enrichment analysis (GSEA) and single-cell cellular functional state analysis were performed.Twenty thousand five hundred thirty genes with bulk RNA-seq data in TCGA were subjected to screening. Preliminary screening identified 10 candidate progression-related genes, including CDH19, AQP5, SDR16C5, NCAN, TTYH1, XAGE2, RIMS2, GZMB, LY6D, and FAM3B. By checking their profiles using single-cell RNA-seq data, only CDH19, SDR16C5, TTYH1, and RIMS2 had expression in primary triple-negative breast cancer (TNBC) cells. Prognostic analysis only confirmed that RIMS2 expression was an independent prognostic indicator of favorable progression free survival (PFS) (HR: 0.78, 95%: 0.64-0.95, P = .015). GSEA analysis showed that low RIMS2 group expression had genes significantly enriched in DNA Repair, and MYC Targets V2. Among the 89 basal-like cells, RIMS2 expression was negatively correlated with DNA repair and epithelial-to-mesenchymal transition (EMT).RIMS2 expression was negatively associated with DNA repair capability of basal-like breast tumor cells and might serve as an independent indicator of favorable PFS.", "claims": [{"id": "claim-method", "statement": "The prognostic significance of the candidate progression-related genes in patients with basal-like tumors was examined by performing Kaplan–Meier survival analysis using the Kaplan–Meier plotter (http://kmplot.com/analysis/), which is an online tool for survival analysis based on over 1800 patients collected from different GEO datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33879671", "locator": "sections[6] \"Meta-analysis-based prognostic analysis using the Kaplan–Meier plotter\" paragraph 2", "quote": "The prognostic significance of the candidate progression-related genes in patients with basal-like tumors was examined by performing Kaplan–Meier survival analysis using the Kaplan–Meier plotter (http://kmplot.com/analysis/), which is an online tool for survival analysis based on over 1800 patients collected from different GEO datasets."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this published article [and its supplementary information files].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33879671", "locator": "sections[18] \"Footnotes\" paragraph 2", "quote": "All data generated or analyzed during this study are included in this published article [and its supplementary information files]."}], "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:33879671"], "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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