Identification of androgen-responsive lncRNAs as diagnostic and prognostic markers for prostate cancer.

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In this study, we firstly conducted analysis of global lncRNA expression patterns by using our own cohort (GSE73397) and two public available gene expression datasets: The Cancer Genome Atlas (TCGA) and GSE55909. Next, we performed microarray to observe genome-wide lncRNAs' expressions under dihydrotestosterone (DHT) stimulation in LNCaP cells (GSE72866), and overlapped the result with ChIPBase data to predict androgen-responsive lncRNAs with ARE. Combined the two results, a total of 44 androgen-responsive lncRNAs with ARE were found to be over-expressed in PCa samples. Ten lncRNAs were selected for further validation by examining their expressions in LNCaP cells under DHT stimulation, and in PCa samples and cell lines. Among them, RP1-4514.2, LINC01138, SUZ12P1 and KLKP1 were validated as directly AR-targeted lncRNAs by ChIP-PCR. Then we conducted a bioinformatic analysis to identify lncRNAs as putative prognostic and therapeutic targets by using TCGA data. Three androgen-responsive lncRNAs, LINC01138, SUZ12P1 and SNHG1 showed association with gleason score and pT-stage. The biological functions of LINC01138 and SUZ12P1 were also evaluated, both lncRNAs promoted the proliferation and inhibited apoptosis of PCa. These results provide potent information for exploring potential biomarkers and therapeutic targets for prostate cancer, especially for castration-resistant PCa.", "claims": [{"id": "claim-method", "statement": "Statistical comparisons between groups of normalized data were performed using T-test or Mann–Whitney U-test according to the test condition.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27556357", "locator": "sections[20] \"Statistical analysis\" paragraph 2", "quote": "Statistical comparisons between groups of normalized data were performed using T-test or Mann–Whitney U-test according to the test condition."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw microarray data were uploaded to the Gene Expression Omnibus public repository (http://www.ncbi.nlm.nih.gov/geo/; Gene Expression Omnibus series no. 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GSE73397)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using T-tests or Mann–Whitney U-tests at p < 0.05, the study integrated GSE73397, TCGA, GSE55909, DHT-stimulated LNCaP microarray data (GSE72866), and ChIPBase to identify 44 androgen-responsive lncRNAs with ARE that were overexpressed in prostate cancer samples.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:27556357", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "we firstly conducted analysis of global lncRNA expression patterns by using our own cohort (GSE73397) and two public available gene expression datasets: The Cancer Genome Atlas (TCGA) and GSE55909."}, {"asset": "source:pmid:27556357", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Next, we performed microarray to observe genome-wide lncRNAs' expressions under dihydrotestosterone (DHT) stimulation in LNCaP cells (GSE72866), and overlapped the result with ChIPBase data to predict androgen-responsive lncRNAs with ARE."}, {"asset": "source:pmid:27556357", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Combined the two results, a total of 44 androgen-responsive lncRNAs with ARE were found to be over-expressed in PCa samples."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using T-tests or Mann–Whitney U-tests at p < 0.05, the study integrated GSE73397, TCGA, GSE55909, DHT-stimulated LNCaP microarray data (GSE72866), and ChIPBase to identify 44 androgen-responsive lncRNAs with ARE that were overexpressed in prostate cancer samples.", "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:27556357"], "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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Next, we performed microarray to observe genome-wide lncRNAs' expressions", "fferentially expressed lncRNAs identified by microarray analysis was shown in Table 1. Hierarchical", "NAs in prostate cancer samples identified by microarray analysis Comprehensive analysis of different", "were analyzed. According to OE Human lncRNA Microarray V2.0, which contains 4321 lncRNAs with descr"], "order_basis": "paper_text_order:472", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["NAs promoted the proliferation and inhibited apoptosis of PCa. 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All of these lncRNAs except"], "order_basis": "paper_text_order:6988", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["passages below 30. The four prostate cancer cell lines were maintained in RPMI 1640 medium (Corning, USA) supplemen"], "order_basis": "paper_text_order:11351", "id": "assay:5"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Kaplan-Meier"], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}