Novel Biomarkers Associated With Progression and Prognosis of Bladder Cancer Identified by Co-expression Analysis.

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Firstly, we used the Gene Expression Omnibus (GEO) dataset GSE37815 to screen differentially expressed genes (DEGs). Secondly, we used the DEGs to construct a co-expression network by weighted gene co-expression network analysis (WGCNA) in GSE71576. We then screened the brown module, which was significantly correlated with the histologic grade (r = 0.85, p = 1e-12) of BC. We conducted functional annotation on all genes of the brown module and found that the genes of the brown module were mainly significantly enriched in \"cell cycle\" correlation pathways. Next, we screened out two real hub genes (ANLN, HMMR) by combining WGCNA, protein-protein interaction (PPI) network and survival analysis. Finally, we combined the GEO datasets (GSE13507, GSE37815, GSE31684, GSE71576). Oncomine, Human Protein Atlas (HPA), and The Cancer Genome Atlas (TCGA) dataset to confirm the predict value of the real hub genes for BC progression and prognosis. A gene-set enrichment analysis (GSEA) revealed that the real hub genes were mainly enriched in \"bladder cancer\" and \"cell cycle\" pathways. A survival analysis showed that they were of great significance in predicting the prognosis of BC. In summary, our study screened and confirmed that two biomarkers could accurately predict the progression and prognosis of BC, which is of great significance for both stratification therapy and the mechanism study of BC.", "claims": [{"id": "claim-method", "statement": "After that, we performed a Kaplan-Meier survival analysis of hub genes in each cohort using the “survival” R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31681575", "locator": "sections[9] \"Verify the Expression Pattern and the Prognostic Value of Real Hub Genes\" paragraph 2", "quote": "After that, we performed a Kaplan-Meier survival analysis of hub genes in each cohort using the “survival” R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. 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"section_index": 3, "section_title": "Data Collection and Study Design", "row_count": 25, "column_count": 6}, "table": {"label": "Table 1", "caption": "Information of datasets used in this study.", "rows": [["Datasets", "GSE37815", "GSE71576", "GSE13507", "GSE31684", "TCGA"], ["", "Training validation datasets", "External validation datasets"], ["Platform", "Illumina human-6 v2.0", "Affymetrix human gene 1.0 ST", "Illumina human-6 v2.0", "Affymetrix human genome U133 plus 2.0", "Illumina RNASeqV2"], ["SAMPLE NUMBER"], ["Total", "18", "44", "256", "93", "427"], ["Bladder cancer", "6", "44", "165", "93", "408"], ["Normal bladder", "–", "0", "68", "0", "19"], ["Recurrent bladder cancer", "–", "–", "23", "–", "–"], ["pStage I", "–", "–", "–", "10", "2"], ["pStageII", "–", "–", "–", "17", "130"], ["pStage III", "–", "–", "–", "42", "140"], ["pStage IV", "–", "–", "–", "19", "135"], ["Unknown stage", "–", "–", "0", "5", "1"], ["Grade I", "–", "14", "105", "–", "–"], ["GradeII", "–", "11", "60", "–", "–"], ["Grade III", "–", "17", "0", "–", "–"], ["High grade", "–", "–", "–", "87", "385"], ["Low grade", "–", "–", "–", "6", "22"], ["Unknown grade", "–", "2", "–", "–", "1"], ["Ta", "–", "27", "24", "–", "–"], ["T1", "–", "6", "80", "–", "–"], ["T2", "–", "3", "31", "–", "–"], ["T3", "–", "2", "19", "–", "–"], ["T4", "–", "4", "11", "–", "–"], ["Unknown T stage", "–", "2", "–", "–", "–"]], "row_count": 25, "column_count": 6, "numeric_cells": 57, "header_rows": 3, "locator": "section[3]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:31681575:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:cd80c09df843f3ab50d53f3fbe340d4bf82f155a455282022de29a4c81f2448d", "bytes": 1267, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#T2", "version": null, "note": "Results of GSEA analysis based on the expression level of hub genes.", 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