Prognostic role of TSPAN1, KIAA1324 and ESRP1 in prostate cancer.

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Based on differentially expressed genes found in a previous study, 84 genes were further validated using mRNA expression data and follow-up information from the Cancer Genome Atlas (TCGA) prostate cancer cohort (n = 497). Immunohistochemistry was used for validation of three genes in an independent, clinically annotated prostatectomy patient cohort (n = 175) with biochemical relapse as endpoint. Also, associations with clinicopathological variables were evaluated. Eleven protein-coding genes from the list of 84 genes were associated with biochemical recurrence-free survival on mRNA expression level in multivariate Cox-analyses. Three of these genes (TSPAN1, ESRP1 and KIAA1324) were immunohistochemically validated using an independent cohort of prostatectomy patients. Both ESRP1 and KIAA1324 were independently associated with biochemical recurrence-free survival. TSPAN1 was univariately prognostic but failed significance on multivariate analysis, probably due to its strong correlation with high Gleason scores. Multistep filtering using the publicly available TCGA cohort, data of an earlier expression profiling study which profiled 3023 cancer-associated transcripts in 42 primary prostate cancer cases, identified two novel candidate prognostic markers (ESRP1 and KIAA1324) of primary prostate cancer for further study.", "claims": [{"id": "claim-method", "statement": "For automatized processing of TCGA data, following pipeline was developed in R: (1) differential gene expression analysis for normal versus tumour samples (R‐packages: TCGAbiolinks, edgeR; false discovery rate (FDR) correction); (2) best cut‐off selection for mRNA expression data dichotomization for selected genes (Principle: systematic test of every available cut‐off for every gene in univariate Cox regression model with biochemical recurrence as endpoint; R‐package: survMisc); (3) automatized processing in univariate Cox regression models of selected genes using best cut‐offs for mRNA expression, rendering of Kaplan–Meier curves with log‐rank test; (4) automatized processing in multivariate Cox regression models of selected genes with predefined set of clinicopathological variables.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33455017", "locator": "sections[11] \"Bioinformatics, statistics\" paragraph 2", "quote": "For automatized processing of TCGA data, following pipeline was developed in R: (1) differential gene expression analysis for normal versus tumour samples (R‐packages: TCGAbiolinks, edgeR; false discovery rate (FDR) correction); (2) best cut‐off selection for mRNA expression data dichotomization for selected genes (Principle: systematic test of every available cut‐off for every gene in univariate Cox regression model with biochemical recurrence as endpoint; R‐package: survMisc); (3) automatized processing in univariate Cox regression models of selected genes using best cut‐offs for mRNA expression, rendering of Kaplan–Meier curves with log‐rank test; (4) automatized processing in multivariate Cox regression models of selected genes with predefined set of clinicopathological variables."}], "state": "complete"}, {"id": "claim-data-access", "statement": "TCGA normalized mRNA expression data (Illumina HiSeq 2000 RNA Sequencing platform, version 2, data version 28.01.2016) and clinical data were extracted for 497 patients in a prostatectomy cohort with the full spectrum of stages and grades.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33455017", "locator": "sections[5] \"Extraction and preparation of TCGA data\" paragraph 2", "quote": "TCGA normalized mRNA expression data (Illumina HiSeq 2000 RNA Sequencing platform, version 2, data version 28.01.2016) and clinical data were extracted for 497 patients in a prostatectomy cohort with the full spectrum of stages and grades."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Both ESRP1 and KIAA1324 were independently associated with biochemical recurrence‐free survival.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:33455017", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Both ESRP1 and KIAA1324 were independently associated with biochemical recurrence‐free survival."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Both ESRP1 and KIAA1324 were independently associated with biochemical recurrence‐free survival.", "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:33455017"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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