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pmid:34285549
Signature Panel of 11 Methylated mRNAs and 3 Methylated lncRNAs for Prediction of Recurrence-Free Survival in Prostate Cancer Patients.
Jiarong Cai · Fei Yang · Xuelian Chen · He Huang · Bin Miao
Pharmacogenomics and personalized medicine · 2021 doi:10.2147/PGPM.S312024
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Complete file
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Therefore, there is a great need to early screen those patients to specifically schedule adjuvant therapy to improve the recurrence-free survival (RFS) rate. This study aims to develop a biomarker to predict RFS for patients with PCa based on the data of methylation, an important heritable contributor to carcinogenesis.\nMETHODS: Methylation expression data of PCa patients were downloaded from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus database (GSE26126), and the European Bioinformatics Institute (E-MTAB-6131). The stable co-methylation modules were identified by weighted gene co-expression network analysis. The genes in modules were overlapped with differentially methylated RNAs (DMRs) screened by MetaDE package in three datasets, which were used to screen the prognostic genes using least absolute shrinkage and selection operator analyses. The prognostic performance of the prognostic signature was assessed by survival curve analysis.\nRESULTS: Five co-methylation modules were considered preserved in three datasets. A total of 192 genes in these 5 modules were overlapped with 985 DMRs, from which a signature panel of 11 methylated messenger RNAs and 3 methylated long non-coding RNAs was identified. This signature panel could independently predict the 5-year RFS of PCa patients, with an area under the receiver operating characteristic curve (AUC) of 0.969 for the training TCGA dataset and 0.811 for the testing E-MTAB-6131 dataset, both of which were higher than the predictive accuracy of Gleason score (AUC = 0.689). Also, the patients with the same Gleason score (6-7 or 8-10) could be further divided into the high-risk group and the low-risk group.\nCONCLUSION: These results suggest that our prognostic model may be a promising biomarker for clinical prediction of RFS in PCa patients.", "claims": [{"id": "claim-method", "statement": "Based on all shared methylated RNAs in TCGA (training), GSE26126 (testing), and E-MTAB-6131 (testing) datasets, co-methylation networks were constructed using the weighted gene co-expression network analysis (WGCNA) software (v1.61; https://cran.r-project.org/web/packages/WGCNA/index.html).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34285549", "locator": "sections[4] \"Identification of Co-Methylation Modules\" paragraph 2", "quote": "Based on all shared methylated RNAs in TCGA (training), GSE26126 (testing), and E-MTAB-6131 (testing) datasets, co-methylation networks were constructed using the weighted gene co-expression network analysis (WGCNA) software (v1.61; https://cran.r-project.org/web/packages/WGCNA/index.html)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data were downloaded from TCGA (https://portal.gdc.cancer.gov/), GEO (GSE26126; http://www. ncbi.nlm.nih.gov/geo/) and EMBL-EBI (E-MTAB-6131; https://www.ebi.ac.uk).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34285549", "locator": "sections[17] \"Data Sharing Statement\" paragraph 2", "quote": "All data were downloaded from TCGA (https://portal.gdc.cancer.gov/), GEO (GSE26126; http://www. ncbi.nlm.nih.gov/geo/) and EMBL-EBI (E-MTAB-6131; https://www.ebi.ac.uk)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:34285549"], "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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"Turquoise", "Upregulated", "0.541", "0.169–0.815", "4.41E-02", "−0.0112"], ["HCP5", "lncRNA", "Turquoise", "Downregulated", "0.367", "0.095–0.423", "1.05E-02", "−0.1128"], ["NAV1", "mRNA", "Turquoise", "Downregulated", "0.117", "0.0184–0.739", "2.30E-02", "−0.1493"], ["HOXA13", "mRNA", "Turquoise", "Downregulated", "0.224", "0.0509–0.987", "4.80E-02", "−0.2229"], ["HAS2", "mRNA", "Turquoise", "Downregulated", "0.170", "0.0308–0.938", "4.20E-02", "−0.5077"], ["CBX2", "mRNA", "Turquoise", "Downregulated", "0.011", "0.000507–0.216", "3.10E-03", "−0.6602"], ["HIST1H2AJ", "mRNA", "Turquoise", "Downregulated", "0.002", "0.000844–0.503", "2.70E-02", "−1.0755"], ["SNX4", "mRNA", "Yellow", "Downregulated", "0.755", "0.138–0.941", "2.30E-02", "−2.3318"]], "row_count": 16, "column_count": 8, "numeric_cells": 58, "header_rows": 2, "locator": "section[11]/table-wrap[1]#t0002"}}, {"id": "asset:table:pmid:34285549:4", "role": "table", "format": "jats-table", "media_type": 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["Pathologic_M (M0/M1/-)", "354/2/19", "6.115", "0.893–16.35", "8.49E-01", "-", "-", "-"], ["Pathologic_N (N0/N1/-)", "273/54/48", "1.691", "0.853–3.353", "1.51E-01", "-", "-", "-"], ["Pathologic_T (T2/T3/T4/-)", "144/219/6/6", "2.865", "1.586–5.177", "4.22E-04", "0.976", "0.457–2.085", "9.51E-01"], ["Radiation therapy (Yes/No/-)", "50/317/8", "2.189", "1.080–4.438", "4.40E-02", "1.006", "0.424–2.388", "9.88E-01"], ["Targeted molecular therapy (Yes/No/-)", "324/42/9", "2.522", "1.276–4.986", "5.85E-03", "0.761", "0.325–1.776", "5.26E-01"], ["Gleason score (6/7/8/9/10)", "37/181/55/98/4", "2.57", "1.858–3.554", "4.89E-10", "2.196", "1.451–3.322", "1.99E-04"], ["Prostate-specific antigen", "1.51 ± 3.17", "1.057", "1.020–1.095", "4.43E-04", "1.016", "0.978–1.055", "4.16E-01"], ["Risk score status (High/Low)", "187/188", "18.72", "5.800–60.43", "3.52E-13", "12.67", "3.845–41.82", "3.02E-05"]], "row_count": 11, "column_count": 8, "numeric_cells": 58, "header_rows": 2, "locator": "section[11]/table-wrap[2]#t0003"}}, {"id": "asset:table:pmid:34285549:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:4168078bc5f3b0b1a4d08da21c29e5af7e76d8ae93b3a61831fe6c8c90dafeda", "bytes": 1473, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#t0004", "version": null, "note": "The RNA Expression Levels of Prognostic Genes", "structure": {"pmcid": "PMC8285280", "section_index": 13, "section_title": "Validation of the RNA Expression Levels of Prognostic Genes", "row_count": 16, "column_count": 8}, "table": {"label": "Table 4", "caption": "The RNA Expression Levels of Prognostic Genes", "rows": [["Symbol", "Type", "Recurrence vs Non-Recurrence", "Tumor vs Control"], ["Log2FC", "P-value", "FDR", "Log2FC", "P-value", "FDR"], ["MEG3", "lncRNA", "0.166016", "0.0313", "0.2537", "−0.35998", "1.04E-03", "0.008423"], ["MMP7", 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