Unbiased data mining identifies cell cycle transcripts that predict non-indolent Gleason score 7 prostate cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30616540", "kind": "science-record", "revision": 6, "content_hash": "sha256:70c829e3f73d13deec124710854f68dedf98faf8f0887b9aeddedf17221aee3e", "created_at": "2026-11-01T15:40:40Z", "updated_at": "2026-11-01T21:21:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Unbiased data mining identifies cell cycle transcripts that predict non-indolent Gleason score 7 prostate cancer.", "doi": "10.1186/s12894-018-0433-5", "pmid": "30616540", "authors": ["Wendy L Johnston", "Charles N Catton", "Carol J Swallow"], "journal": "BMC urology", "year": 2019, "abstract": "BACKGROUND: Patients with newly diagnosed non-metastatic prostate adenocarcinoma are typically classified as at low, intermediate, or high risk of disease progression using blood prostate-specific antigen concentration, tumour T category, and tumour pathological Gleason score. Classification is used to both predict clinical outcome and to inform initial management. However, significant heterogeneity is observed in outcome, particularly within the intermediate risk group, and there is an urgent need for additional markers to more accurately hone risk prediction. Recently developed web-based visualization and analysis tools have facilitated rapid interrogation of large transcriptome datasets, and querying broadly across multiple large datasets should identify predictors that are widely applicable.\nMETHODS: We used camcAPP, cBioPortal, CRN, and NIH NCI GDC Data Portal to data mine publicly available large prostate cancer datasets. A test set of biomarkers was developed by identifying transcripts that had: 1) altered abundance in prostate cancer, 2) altered expression in patients with Gleason score 7 tumours and biochemical recurrence, 3) correlation of expression with time until biochemical recurrence across three datasets (Cambridge, Stockholm, MSKCC). Transcripts that met these criteria were then examined in a validation dataset (TCGA-PRAD) using univariate and multivariable models to predict biochemical recurrence in patients with Gleason score 7 tumours.\nRESULTS: Twenty transcripts met the test criteria, and 12 were validated in TCGA-PRAD Gleason score 7 patients. Ten of these transcripts remained prognostic in Gleason score 3 + 4 = 7, a sub-group of Gleason score 7 patients typically considered at a lower risk for poor outcome and often not targeted for aggressive management. All transcripts positively associated with recurrence encode or regulate mitosis and cell cycle-related proteins. The top performer was BUB1, one of four key MIR145-3P microRNA targets upregulated in hormone-sensitive as well as castration-resistant PCa. SRD5A2 converts testosterone to its more active form and was negatively associated with biochemical recurrence.\nCONCLUSIONS: Unbiased mining of large patient datasets identified 12 transcripts that independently predicted disease recurrence risk in Gleason score 7 prostate cancer. The mitosis and cell cycle proteins identified are also implicated in progression to castration-resistant prostate cancer, revealing a pivotal role for loss of cell cycle control in the latter.", "claims": [{"id": "claim-method", "statement": "Univariate logistic regression (SAS 9.4) was performed to determine odds ratios (ORs), and ROC-AUC was calculated for each of the test transcripts, as well as for Gleason score and pre-operative PSA using easyROC http://www.biosoft.hacettepe.edu.tr/easyROC/ [36]. Multivariable logistic regression was performed on transcripts with increased abundance and ORs having p values < 0.05, and SRD5A2, which had decreased abundance, in Gleason score 7 (n = 158), Gleason score 4 + 3 = 7 (n = 70) and Gleason score 3 + 4 = 7 (n = 88) tumours.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30616540", "locator": "sections[2] \"Methods\" paragraph 3", "quote": "Univariate logistic regression (SAS 9.4) was performed to determine odds ratios (ORs), and ROC-AUC was calculated for each of the test transcripts, as well as for Gleason score and pre-operative PSA using easyROC http://www.biosoft.hacettepe.edu.tr/easyROC/ [36]. Multivariable logistic regression was performed on transcripts with increased abundance and ORs having p values < 0.05, and SRD5A2, which had decreased abundance, in Gleason score 7 (n = 158), Gleason score 4 + 3 = 7 (n = 70) and Gleason score 3 + 4 = 7 (n = 88) tumours."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data analysed in this study are publicly available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30616540", "locator": "sections[9] \"ack\" paragraph 1", "quote": "All data analysed in this study are publicly available."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:30616540"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30616540", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12894-018-0433-5", "sha256": "sha256:4a636a464aead4a0e8011b84608d8aaebdbe0d9925bcc7dd07bcae177c8c5fb2", "bytes": 35426, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12894-018-0433-5", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6322345", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:30616540:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:88b291834fe8b3b4771fd2b0eb796660b5bbdbbfa46ed4ec36f29d0c609a6799", "bytes": 2310, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#Tab1", "version": null, "note": "Test set of 20 transcripts that predicted time until BCR", "structure": {"pmcid": "PMC6322345", "section_index": 3, "section_title": "Results", "row_count": 24, "column_count": 9}, "table": {"label": "Table 1", "caption": "Test set of 20 transcripts that predicted time until BCR", "rows": [["", "", "", "Cambridge (n = 111)", "Stockholm (n = 92)", "MSKCC (n = 140)"], ["Transcript*", "Chromosomal location", "Fold changec", "p value", "RP cutoff d", "p value", "RP cutoff d", "p value", "RP cutoff d"], ["TPX2", "20q11.21", "3.0", "4.80E-05", "< 6.96", "5.40E-02", "< 6.45", "5.10E-07", "< 6.38"], ["BUB1", "2q13", "2.8", "1.10E-02", "< 6.26", "9.10E-03", "< 6.36", "9.40E-07", "< 6.27"], ["CCNA2", "4q27", "2.5", "1.00E-02", "< 6.99", "8.70E-03", "< 7.16", "6.70E-06", "< 6.91"], ["E2F2", "1p36.12", "1.9", "2.90E-03", "< 7.04", "4.10E-02", "< 6.62", "1.40E-02", "< 9.99"], ["UBE2C", "20q13.12", "3.4", "1.80E-03", "< 7.52", "5.80E-03", "< 8.15", "2.00E-06", "< 6.62"], ["NCAPG", "4p15.31", "2.7", "2.70E-02", "< 6.63", "4.60E-03", "< 6.77", "5.50E-07", "< 6.02"], ["CDK1", "10q21.2", "2.1", "3.70E-03", "< 7.13", "2.20E-03", "< 7.13", "1.40E-04", "< 4.95"], ["CDKN3", "14q22.2", "2.4", "1.50E-02", "< 6.83", "4.50E-03", "< 7.01", "1.60E-07", "< 5.12"], ["DLGAP5", "14q22.3", "3.4", "4.90E-03", "< 6.61", "1.90E-02", "< 6.63", "2.90E-06", "< 5.45"], ["MELK", "9p13.2", "3.3", "2.40E-02", "< 6.97", "6.60E-04", "< 6.45", "3.50E-06", "< 5.6"], ["CCNB1", "5q13.2", "1.8", "1.60E-02", "< 7.05", "3.00E-03", "< 6.83", "4.30E-04", "< 6.98"], ["TMEM206", "1q32.3", "1.3", "2.90E-02", "< 7.87", "1.30E-02", "< 7.22", "2.50E-03", "< 7.66"], ["SHMT2", "12q13.3", "1.7", "3.20E-02", "< 10.4", "3.50E-02", "< 10.1", "1.10E-03", "< 8.57"], ["ANKMY1 a", "2q37.3", "1.03", "4.90E-02", "< 7.77", "2.20E-03", "> 7.29", "2.70E-03", "< 8.11"], ["SRD5A2", "2p23.1", "− 3.7", "9.10E-03", "> 7.11", "1.70E-03", "> 6.53", "1.60E-07", "> 7.05"], ["CSRP1", "1q32.1", "−2.9", "1.60E-02", "> 12", "2.30E-02", "> 10.9", "2.00E-05", "> 9.55"], ["NFIB", "9p23-p22.3", "− 1.1", "7.30E-03", "> 11.5", "1.90E-02", "> 11.15", "1.80E-04", "> 9.23"], ["PGM5", "9q21.11", "−3.6", "5.70E-03", "> 8.59", "9.30E-03", "> 10.8", "4.10E-07", "> 7.97"], ["CNN1", "19p13.2", "−3.1", "1.40E-02", "> 8.99", "3.00E-02", "> 8.72", "2.40E-07", "> 8.72"], ["DES", "2q35", "−3.1", "2.40E-02", "> 9.53", "4.70E-02", "> 8.32", "2.70E-05", "> 8.99"], ["MPDZ", "9p23", "−1.4", "1.10E-02", "> 8.22", "1.10E-02", "> 7.44", "3.40E-03", "> 8.43"], ["ALDH1A2 b", "15q21.3", "− 3.2", "3.30E-02", "> 8.47", "2.50E-02", "> 7.55", "6.40E-07", "> 7.19"]], "row_count": 24, "column_count": 9, "numeric_cells": 180, "header_rows": 2, "locator": "section[3]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:30616540:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:62c578829b4147047550f984da19613a69809fb5bf056061ee7a587effb8dcfd", "bytes": 2255, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[2]#Tab2", "version": null, "note": "Univariate logistic regression and ROC-AUC analyses for predicting BCR in patients with Gleason score 7 tumours", "structure": {"pmcid": "PMC6322345", "section_index": 3, "section_title": "Results", "row_count": 20, "column_count": 12}, "table": {"label": "Table 2", "caption": "Univariate logistic regression and ROC-AUC analyses for predicting BCR in patients with Gleason score 7 tumours", "rows": [["Variable", "Odds Ratio (OR)", "95% CI OR", "P value OR", "ROC-AUC", "SE AUC", "P value AUC", "Youden cut-off", "Sensitivity", "Specificity", "PPV", "NPV"], ["(up in tumour)"], ["BUB1", "1.31", "0.908–1.889", "1.48E-01", "0.720", "0.055", "5.35E-05", "1.22", "0.92", "0.58", "0.16", "0.99"], ["TPX2", "1.18", "0.994–1.406", "5.79E-02", "0.732", "0.066", "4.53E-04", "3.54", "0.85", "0.64", "0.18", "0.98"], ["NCAPG", "1.51", "0.913–2.510", "1.08E-01", "0.711", "0.065", "1.08E-03", "0.94", "0.92", "0.48", "0.14", "0.99"], ["UBE2C", "1.07", "0.998–1.142", "5.60E-02", "0.713", "0.067", "1.42E-03", "7.79", "0.69", "0.69", "0.17", "0.96"], ["MELK", "1.21", "0.908–1.612", "1.93E-01", "0.687", "0.065", "3.97E-03", "1.82", "0.69", "0.69", "0.17", "0.96"], ["CCNA2", "1.27", "0.967–1.680", "8.57E-02", "0.694", "0.069", "5.04E-03", "2.58", "0.69", "0.70", "0.17", "0.96"], ["CCNB1", "1.13", "0.954–1.345", "1.56E-01", "0.685", "0.066", "5.20E-03", "4.60", "0.92", "0.48", "0.14", "0.99"], ["CDK1", "1.07", "0.969–1.181", "1.81E-01", "0.691", "0.070", "6.27E-03", "4.97", "0.77", "0.62", "0.15", "0.97"], ["E2F2", "2.84", "0.715–11.309", "1.38E-01", "0.682", "0.068", "7.55E-03", "0.37", "0.77", "0.63", "0.16", "0.97"], ["DLGAP5", "1.24", "0.766–2.014", "3.80E-01", "0.657", "0.070", "2.54E-02", "0.65", "0.85", "0.46", "0.12", "0.97"], ["TMEM206", "1.15", "0.999–1.321", "5.10E-02", "0.672", "0.086", "4.51E-02", "9.11", "0.85", "0.52", "0.14", "0.97"], ["CDKN3", "1.14", "0.936–1.387", "1.93E-01", "0.643", "0.079", "6.93E-02", "2.04", "0.92", "0.39", "0.12", "0.98"], ["SHMT2", "1.01", "0.990–1.038", "2.52E-01", "0.605", "0.069", "1.25E-01", "56.64", "0.69", "0.57", "0.13", "0.95"], ["(down in tumour)"], ["SRD5A2", "0.90", "0.786–1.021", "9.85E-02", "0.674", "0.079", "2.70E-02", "7.98", "0.92", "0.44", "0.13", "0.99"], ["CSRP1", "0.998", "0.996–1.001", "1.30E-01", "0.628", "0.080", "1.11E-01", "417.97", "0.54", "0.72", "0.15", "0.95"], ["PGM5", "0.99", "0.974–1.006", "2.04E-01", "0.592", "0.085", "2.84E-01", "22.95", "0.39", "0.81", "0.15", "0.94"], ["NFIB", "0.98", "0.941–1.029", "4.68E-01", "0.584", "0.092", "3.60E-01", "27.09", "0.69", "0.56", "0.12", "0.95"]], "row_count": 20, "column_count": 12, "numeric_cells": 189, "header_rows": 1, "locator": "section[3]/table-wrap[2]#Tab2"}}, {"id": "asset:table:pmid:30616540:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:173231592c7aef70eb243e43cff0859e1b139cd18e5bbc71e6ed15913ef95b6c", "bytes": 2279, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[3]#Tab3", "version": null, "note": "Univariate logistic regression and ROC-AUC analyses for predicting BCR in patients with Gleason score 3 + 4 = 7 tumours", "structure": {"pmcid": "PMC6322345", "section_index": 3, "section_title": "Results", "row_count": 20, "column_count": 12}, "table": {"label": "Table 3", "caption": "Univariate logistic regression and ROC-AUC analyses for predicting BCR in patients with Gleason score 3 + 4 = 7 tumours", "rows": [["Variable", "Odds Ratio (OR)", "95% CI OR", "P value OR", "ROC-AUC", "SE AUC", "P value AUC", "Youden cut-off", "Sensitivity", "Specificity", "PPV", "NPV"], ["(up in tumour)"], ["BUB1", "1.93", "1.029–3.604", "4.03E-02", "0.865", "0.045", "4.75E-16", "1.54", "1.000", "0.78", "0.22", "1.00"], ["TPX2", "1.40", "1.055–1.852", "1.98E-02", "0.872", "0.060", "5.07E-10", "4.09", "1.000", "0.74", "0.19", "1.00"], ["NCAPG", "2.72", "1.071–6.915", "3.55E-02", "0.855", "0.067", "1.23E-07", "1.33", "0.800", "0.83", "0.22", "0.99"], ["UBE2C", "1.20", "1.051–1.369", "7.00E-03", "0.889", "0.050", "7.21E-15", "7.79", "1.000", "0.80", "0.23", "1.00"], ["MELK", "1.72", "0.939–3.152", "7.89E-02", "0.819", "0.082", "1.03E-04", "2.17", "0.800", "0.86", "0.25", "0.99"], ["CCNA2", "1.83", "1.113–3.000", "1.71E-02", "0.810", "0.106", "3.39E-03", "2.63", "0.800", "0.80", "0.19", "0.99"], ["CCNB1", "1.63", "1.109–2.383", "1.27E-02", "0.824", "0.083", "1.00E-04", "4.69", "1.000", "0.57", "0.12", "1.00"], ["CDK1", "1.28", "1.070–1.532", "6.80E-03", "0.863", "0.090", "5.50E-05", "7.32", "0.800", "0.90", "0.33", "0.99"], ["E2F2", "5.98", "0.824–43.408", "7.70E-02", "0.720", "0.119", "6.39E-02", "0.37", "0.800", "0.70", "0.14", "0.98"], ["DLGAP5", "1.95", "0.954–3.984", "6.73E-02", "0.855", "0.066", "6.61E-08", "0.86", "1.000", "0.64", "0.14", "1.00"], ["TMEM206", "0.98", "0.766–1.243", "8.40E-01", "0.545", "0.154", "7.72E-01", "9.11", "0.800", "0.52", "0.09", "0.98"], ["CDKN3", "1.50", "1.071–2.108", "1.85E-02", "0.708", "0.187", "2.65E-01", "6.47", "0.600", "0.95", "0.43", "0.98"], ["SHMT2", "1.03", "0.983–1.075", "2.21E-01", "0.740", "0.093", "9.94E-03", "60.61", "0.800", "0.71", "0.14", "0.98"], ["(down in tumour)"], ["SRD5A2", "0.58", "0.367–0.921", "2.09E-02", "0.884", "0.079", "1.03E-06", "3.75", "0.800", "0.88", "0.29", "0.99"], ["CSRP1", "1.00", "0.992–1.001", "9.71E-02", "0.752", "0.132", "5.66E-02", "417.97", "0.800", "0.80", "0.19", "0.99"], ["PGM5", "0.97", "0.930–1.007", "1.04E-01", "0.745", "0.136", "7.28E-02", "18.57", "0.600", "0.90", "0.27", "0.97"], ["NFIB", "0.98", "0.903–1.054", "5.26E-01", "0.578", "0.129", "5.45E-01", "24.07", "0.600", "0.72", "0.12", "0.97"]], "row_count": 20, "column_count": 12, "numeric_cells": 189, "header_rows": 1, "locator": "section[3]/table-wrap[3]#Tab3"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "regression_modelling", "specific": "logistic", "label": "Regression modelling", "dsl_operations": ["glm_logit_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Univariate logistic regression (SAS 9.4) was performed to determine odds ratios (ORs), and ROC-AUC was calculated for each of the test transcripts, as well as for Gleason score and pre-operative PSA using easyROC http://www.biosoft.hacettepe.edu.tr/easyROC/ [36]. Multivariable logistic regression was performed on transcripts with increased abundance and ORs having p values < 0.05, and SRD5A2, which had decreased abundance, in Gleason score 7 (n = 158), Gleason score 4 + 3 = 7 (n = 70) and Gleason score 3 + 4 = 7 (n = 88) tumours."}}, {"id": "method-2", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Kaplan-Meier"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["glm_logit_fit"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: logistic."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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