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pmid:33329695
Identification of Tumor Microenvironment-Related Prognostic Biomarkers in Luminal Breast Cancer.
Yanyan Wang · Mingzhi Zhu · Feng Guo · Yi Song · Xunjie Fan · Guijun Qin
Frontiers in genetics · 2020 doi:10.3389/fgene.2020.555865
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Experiment
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Data
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Complete file
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Methods: We obtained immune scores (ISs) and stromal scores (SSs) for The Cancer Genome Atlas (TCGA) luminal BC cohort from the online ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) portal. The relationships between ISs and SSs and the overall survival of luminal BC patients were assessed by the Kaplan-Meier method. The differentially expressed messenger RNAs (DEmRNAs) related to the ISs and SSs were subjected to functional enrichment analysis. Additionally, a competing endogenous RNA (ceRNA) network was constructed with differentially expressed microRNAs (DEmiRNAs) and long noncoding RNAs (DElncRNAs). Furthermore, a protein-protein interaction (PPI) network was established to analyze the DEmRNAs in the ceRNA network. Then, survival analysis of biomarkers involved in the ceRNA network was carried out to explore their prognostic value. Finally, these biomarkers were validated using the luminal BC dataset from the Gene Expression Omnibus (GEO) database. Results: The results showed that ISs were significantly associated with longer survival times of luminal BC patients. Functional enrichment analysis showed that the DEmRNAs were mainly associated with immune response, antigen binding, and the extracellular region. In the PPI network, the top 10 DEmRNAs were identified as hub genes that affected the TME of luminal BC. Finally, two DEmiRNAs, two DElncRNAs, and 17 DEmRNAs of the ceRNA network associated with the TME were shown to have prognostic value. Subsequently, the expression of 15 prognostic biomarkers was validated in one additional dataset (GSE81002). In particular, one lncRNA (GVINP1) and five mRNAs (CCDC69, DOCK2, IKZF1, JCHAIN, and NCKAP1L) were novel biomarkers. Conclusions: Our studies demonstrated that ISs were associated with the survival of luminal BC patients, and a set of novel biomarkers that might play a prognostic role in the TME of luminal BC was identified.", "claims": [{"id": "claim-method", "statement": "The overall survival of these two groups was estimated with the Kaplan-Meier survival estimator, and the corresponding survival outcomes of the two groups were compared by log-rank tests.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33329695", "locator": "sections[4] \"Association Between Immune Scores/Stromal Scores and the Prognoses of Luminal Breast Cancer Patients\" paragraph 2", "quote": "The overall survival of these two groups was estimated with the Kaplan-Meier survival estimator, and the corresponding survival outcomes of the two groups were compared by log-rank tests."}], "state": "complete"}, {"id": "claim-data-access", "statement": "In order to provide an overall estimation of the molecular mechanisms in the TME of luminal BC, we combined RNA-Seq datasets and clinical information of luminal A and luminal B patients from TCGA database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33329695", "locator": "sections[3] \"Data Processing and Estimation of Immune Scores and Stromal Scores\" paragraph 2", "quote": "In order to provide an overall estimation of the molecular mechanisms in the TME of luminal BC, we combined RNA-Seq datasets and clinical information of luminal A and luminal B patients from TCGA database."}], "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:33329695"], "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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