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pmid:32419983
Integrated analysis of lymphocyte infiltration-associated lncRNA for ovarian cancer via TCGA, GTEx and GEO datasets.
Meijing Wu · Xiaobin Shang · Yue Sun · Jing Wu · Guoyan Liu
PeerJ · 2020 doi:10.7717/peerj.8961
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Complete file
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In this study, our aim is to identify lncRNA-associated competing endogenous RNA (ceRNA ) axes that could define more reliable prognostic parameters of HGSOC, and to investigate the lncRNAs' potential mechanism of in lymphocyte infiltration.\nMETHODS: The RNA-seq and miRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database; while for obtaining the differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs), we used edgeR, limma and DESeq2. After validating the RNA, miRNA and gene expressions, using integrated three RNA expression profiles (GSE18520, GSE27651, GSE54388) and miRNA profile (GSE47841) from the Gene Expression Omnibus (GEO) database, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses through ClusterProfiler. The prognostic value of these genes was determined with Kaplan-Meier survival analysis and Cox regression analysis. The ceRNA network was constructed using Cytoscape. The correlation between lncRNAs in ceRNA network and immune infiltrating cells was analyzed by using Tumor IMmune Estimation Resource (TIMER), and gene markers of tumor-infiltrating immune cells were identified using Spearman's correlation after removing the influence of tumor purity.\nRESULTS: A total of 33 DELs (25 upregulated and eight downregulated), 134 DEMs (76 upregulated and 58 downregulated), and 1,612 DEGs (949 upregulated and 663 downregulated) were detected that could be positively correlated with overall survival (OS) of HGSOC. With the 1,612 analyzed genes, we constructed a ceRNA network, which indicated a pre-dominant involvement of the immune-related pathways. Furthermore, our data revealed that LINC00665 influenced the infiltration level of macrophages and dendritic cells (DCs). On the other hand, FTX and LINC00665, which may play their possible roles through the ceRNA axis, demonstrated a potential to inhibit Tregs and prevent T-cell exhaustion.\nCONCLUSION: We defined several prognostic biomarkers for the incidence and progression of HGSOC and constructed a network for ceRNA axes; among which three were indicated to have a positive correlation with lymphocyte infiltration, namely: FTX-hsa-miR-150-5p-STK11, LINC00665-hsa-miR449b-5p-VAV3 and LINC00665-hsa-miR449b-5p-RRAGD.", "claims": [{"id": "claim-method", "statement": "Univariate Cox regression analysis was implemented to perform prognostic analysis using the R survival package (Version 2.43.3; https://cran.r-project.org/package=survival).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32419983", "locator": "sections[7] \"Survival analysis\" paragraph 2", "quote": "Univariate Cox regression analysis was implemented to perform prognostic analysis using the R survival package (Version 2.43.3; https://cran.r-project.org/package=survival)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Raw data is available in the Supplementary Files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32419983", "locator": "sections[21] \"Additional Information and Declarations\" paragraph 4", "quote": "Raw data is available in the Supplementary 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:32419983"], "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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