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pmid:35626146
Gene Expression Monotonicity across Bladder Cancer Stages Informs on the Molecular Pathogenesis and Identifies a Prognostic Eight-Gene Signature.
Rafael Stroggilos · Maria Frantzi · Jerome Zoidakis · Marika Mokou · Napoleon Moulavasilis · Emmanouil Mavrogeorgis · Anna Melidi · Manousos Makridakis · Konstantinos Stravodimos · Maria G Roubelakis · Harald Mischak · Antonia Vlahou
Cancers · 2022 doi:10.3390/cancers14102542
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Here, we leverage publicly available data to characterize bladder cancer (BLCA)'s stage biology based on increased sample sizes, identify potential therapeutic targets, and extract putative biomarkers. A total of 1135 primary BLCA transcriptomes from 12 microarray studies were compiled in a meta-cohort and analyzed for monotonal alterations in pathway activities, gene expression, and co-expression patterns with increasing stage (Ta-T1-T2-T3-T4), starting from the non-malignant tumor-adjacent urothelium. The TCGA-2017 and IMvigor-210 RNA-Seq data were used to validate our findings. Wnt, MTORC1 signaling, and MYC activity were monotonically increased with increasing stage, while an opposite trend was detected for the catabolism of fatty acids, circadian clock genes, and the metabolism of heme. Co-expression network analysis highlighted stage- and cell-type-specific genes of potentially synergistic therapeutic value. An eight-gene signature, consisting of the genes AKAP7, ANLN, CBX7, CDC14B, ENO1, GTPBP4, MED19, and ZFP2, had independent prognostic value in both the discovery and validation sets. This novel eight-gene signature may increase the granularity of current risk-to-progression estimators.", "claims": [{"id": "claim-method", "statement": "Cox proportional hazards regression was performed with the packages survminer and survival, and statistical significance was determined via the log-rank method.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35626146", "locator": "sections[2] \"2. Materials and Methods\" paragraph 12", "quote": "Cox proportional hazards regression was performed with the packages survminer and survival, and statistical significance was determined via the log-rank method."}], "state": "complete"}, {"id": "claim-data-access", "statement": "This study used publicly available data. 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The raw microarrays used here are publicly available in the Gene Expression Omnibus under the accession codes GSE121711, GSE93527, GSE31684, GSE104922, GSE128959, GSE83586, GSE48276, GSE52219, GSE69795, GSE13507, and GSE48075, and in ArrayExpress under the accession code E-MTAB-1940. TCGA-BLCA-2017 molecular and clinical data were downloaded from cBioPortal. IMvigor molecular and clinical data were acquired through the IMvigor210CoreBiologies R package. The processed, ComBat-normalized matrix (discovery set) and the sample clinical data are available as Supplements. The codes used to generate the results and figures are available upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "This study used publicly available data. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE121711", "GSE93527", "GSE31684", "GSE104922", "GSE128959", "GSE83586", "GSE48276", "GSE52219", "GSE69795", "GSE13507", "GSE48075", "E-MTAB-1940"], "resolved_accessions": ["GSE121711", "GSE93527", "GSE31684", "GSE104922", "GSE128959", "GSE83586", "GSE48276", "GSE52219", "GSE69795", "GSE13507", "GSE48075", "E-MTAB-1940"], "statements": ["This study used publicly available data. The raw microarrays used here are publicly available in the Gene Expression Omnibus under the accession codes GSE121711, GSE93527, GSE31684, GSE104922, GSE128959, GSE83586, GSE48276, GSE52219, GSE69795, GSE13507, and GSE48075, and in ArrayExpress under the accession code E-MTAB-1940. TCGA-BLCA-2017 molecular and clinical data were downloaded from cBioPortal. IMvigor molecular and clinical data were acquired through the IMvigor210CoreBiologies R package. 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The TCGA-2017 and IMvigor-210 RNA-Seq data were used to validate our findings. Wnt", "ive biomarkers. A total of 1135 primary BLCA transcriptomes from 12 microarray studies were compiled in", "is focused on primary, treatment-naïve tumor transcriptomes. The selection of datasets and samples eligi", "comprised 1054 primary bladder cancer tumor transcriptomes of treatment-naïve patients without any prio"], "order_basis": "paper_text_order:503", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["of 1135 primary BLCA transcriptomes from 12 microarray studies were compiled in a meta-cohort and a", "ell as the processing and integration of raw microarray data, is detailed in Appendix A. Briefly, we", "tailed in Appendix A. 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