A signature of tumor DNA repair genes associated with the prognosis of surgically-resected lung adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33304656", "kind": "science-record", "revision": 7, "content_hash": "sha256:5cf873b49d55d3a72dbb29607faaad473da4b9b4277040f247b684f6b0022848", "created_at": "2026-11-01T15:41:19Z", "updated_at": "2026-11-01T22:02:42Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A signature of tumor DNA repair genes associated with the prognosis of surgically-resected lung adenocarcinoma.", "doi": "10.7717/peerj.10418", "pmid": "33304656", "authors": ["Xiongtao Yang", "Guohui Wang", "Runchuan Gu", "Xiaohong Xu", "Guangying Zhu"], "journal": "PeerJ", "year": 2020, "abstract": "BACKGROUND: Lung cancer has the highest morbidity and mortality of cancers worldwide. Lung adenocarcinoma (LUAD) is the most common pathological subtype of lung cancer and surgery is its most common treatment. The dysregulated expression of DNA repair genes is found in a variety of cancers and has been shown to affect the origin and progression of these diseases. However, the function of DNA repair genes in surgically-treated LUAD is unclear.\nMETHODS: We sought to determine the association between the signature of DNA repair genes for patients with surgical LUAD and their overall prognosis. We obtained gene expression data and corresponding clinical information of LUAD from The Cancer Genome Atlas (TCGA) database. The differently expressed DNA repair genes of surgically-treated LUAD and normal tissues were identified using the Wilcoxon rank-sum test. We used uni- and multivariate Cox regression analyses to shrink the aberrantly expressed genes, which were then used to construct the prognostic signature and the risk score formula associated with the independent prognosis of surgically-treated LUAD. We used Kaplan-Meier and Cox hazard ratio analyses to confirm the diagnostic and prognostic roles. Two validation sets (GSE31210 and GSE37745) were downloaded from the Gene Expression Omnibus (GEO) and were used to externally verify the prognostic value of the signature. OSluca online database verifies the hazard ratio for the DNA repair genes by which the signature was constructed. We investigated the correlation between the signature of the DNA repair genes and the clinical parameters. The potential molecular mechanisms and pathways of the prognostic signature were explored using Gene Set Enrichment Analysis (GSEA).\nRESULTS: We determined the prognostic signature based on six DNA repair genes (PLK1, FOXM1, PTTG1, CCNO, HIST3H2A, and BLM) and calculated the risk score based on this formula. Patients with surgically-treated LUAD were divided into high-risk and low-risk groups according to the median risk score. The high-risk group showed poorer overall survival than the low-risk group; the signature was used as an independent prognostic indicator and had a greater prognostic value in surgically-treated LUAD. The prognostic value was replicated in GSE31210 and GSE37745. OSluca online database analysis shows that six DNA repair genes were associated with poor prognosis in most lung cancer datasets. The prognostic signature risk score correlated with the pathological stage and smoking status in surgically-treated LUAD. The GSEA of the risk signature in high-risk patients showed pathways associated with the cell cycle, oocyte meiosis, mismatch repair, homologous recombination, and nucleotide excision repair.\nCONCLUSIONS: A six-DNA repair gene signature was determined using TCGA data mining and GEO data verification. The gene signature may serve as a novel prognostic biomarker and therapeutic target for surgically-treated LUAD.", "claims": [{"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:\nThe raw data are available in the Supplementary Files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33304656", "locator": "sections[25] \"Data Availability Statement\" paragraphs 1-3", "quote": "The following information was supplied regarding data availability:\nThe raw data are available in the Supplementary Files."}], "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:33304656"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE31210"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE31210"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33304656", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.10418", "sha256": "sha256:de7784e22175252606bd5d400e88eb45c65ef50d0e8ebe0325d183dc4f4471d9", "bytes": 46288, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.10418", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7700735", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE31210", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31210", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE31210", "version": null, "note": "The following information was supplied regarding data availability:\nThe raw data are 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"media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ffc7d61713c9fc735d8796751bdbda3eab600f1532f645d5219efd2ff5a9f0d4", "bytes": 1296, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#table-1", "version": null, "note": "Clinic pathological characteristics of surgical LUAD patients from the training (TCGA) andvalidation sets (GSE31210, GSE37745).", "structure": {"pmcid": "PMC7700735", "section_index": 3, "section_title": "Data source and preprocessing", "row_count": 26, "column_count": 7}, "table": {"label": "Table 1", "caption": "Clinic pathological characteristics of surgical LUAD patients from the training (TCGA) andvalidation sets (GSE31210, GSE37745).", "rows": [["Characteristics", "TCGA (n = 260)", "GSE31210 (n = 226)", "GSE37745 (n = 106)"], ["", "Number of cases %", "Number of cases %", "Number of cases %"], ["Platform", "", "", "GPL570", "GPL570"], ["Noncancerous samples", "59", "0", "0"], ["Surgically-resected LUAD samples", "201", "226", "106"], ["Age (years)", "", "", "", "", "", ""], ["≥65", "99", "49.3", "62", "27.4", "52", "49.1"], ["<65", "97", "48.3", "164", "72.6", "54", "50.9"], ["Gender", "", "", "", "", "", ""], ["Male", "91", "45.3", "105", "46.5", "46", "43.4"], ["Female", "110", "54.7", "121", "53.5", "60", "56.6"], ["Stage", "", "", "", "", "", ""], ["Stage 2-4", "95", "47.3", "58", "25.7", "36", "34.0"], ["Stage 1", "106", "52.7", "168", "74.3", "70", "66.0"], ["T", "", "", "", "", "", ""], ["T3-4", "30", "14.9", "", "", "", ""], ["T1-2", "169", "84.1", "", "", "", ""], ["N", "", "", "", "", "", ""], ["N1-3", "66", "32.8", "", "", "", ""], ["N0", "128", "63.7", "", "", "", ""], ["M", "", "", "", "", "", ""], ["M1-Mx", "57", "28.4", "", "", "", ""], ["M0", "144", "71.6", "", "", "", ""], ["Smoking", "", "", "", "", "", ""], ["Yes", "", "", "111", "49.1", "", ""], ["No", "", "", "115", "50.9", "", ""]], "row_count": 26, "column_count": 7, "numeric_cells": 70, "header_rows": 2, "locator": "section[3]/table-wrap[1]#table-1"}}, {"id": "asset:table:pmid:33304656:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9dbe2327f8f569e807d08b1e7e2841dbe621196c055548eed8e99c565a471a33", "bytes": 882, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[7]/table-wrap[1]#table-2", "version": null, "note": "The information of 6 prognostic mRNAs importantly associated with overall survival inpatients with surgical LUAD.", "structure": {"pmcid": "PMC7700735", "section_index": 7, "section_title": "Identification of DNA repair-related prognostic genes", "row_count": 7, "column_count": 6}, "table": {"label": "Table 2", "caption": "The information of 6 prognostic mRNAs importantly associated with overall survival inpatients with surgical LUAD.", "rows": [["mRNA", "Ensemble ID", "Location", "Coefficient", "HR", "P-value"], ["PLK1", "ENSG00000166851", "Chr16:23,677,656-23,690,367", "0.555713", "1.743183", "0.043687"], ["FOXM1", "ENSG00000111206", "Chr12: 2,857,681-2,877,155", "−0.5696", "0.565754", "0.024525"], ["PTTG1", "ENSG00000164611", "Chr5: 160,421,855-160,428,739", "0.291471", "1.338395", "0.064214"], ["CCNO", "ENSG00000152669", "Chr5: 55,231,152-55,233,608", "−0.30485", "0.737234", "0.004893"], ["HIST3H2A", "ENSG00000181218", "Chr1: 228,456,979-228,457,873", "−0.17162", "0.842298", "0.030497"], ["BLM", "ENSG00000197299", "Chr15: 90,717,346-90,816,166", "0.442472", "1.556551", "0.119493"]], "row_count": 7, "column_count": 6, "numeric_cells": 30, "header_rows": 1, "locator": "section[7]/table-wrap[1]#table-2"}}], "gaps": ["asset:data:geo:GSE31210 not downloaded", "asset:data:geo:GSE31210 licence not read", "asset:data:geo:GSE37745 not downloaded", "asset:data:geo:GSE37745 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", 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