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pmid:33441161
Identification of a prognostic gene signature of colon cancer using integrated bioinformatics analysis.
Zhengyu Fang · Sumei Xu · Yiwen Xie · Wenxi Yan
World journal of surgical oncology · 2021 doi:10.1186/s12957-020-02116-y
Paper
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Experiment
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Data
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Complete file
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This study aimed to construct a prognostic model for predicting the prognosis of colon cancer.\nMETHODS: The gene expression profile data of colon cancer were obtained from the TCGA, GSE44861, and GSE44076 datasets. The WGCNA module genes and common differentially expressed genes (DEGs) were used to screen out the prognosis-associated DEGs, which were used to construct a prognostic model. The performance of the prognostic model was assessed and validated in the TCGA training and microarray validation sets (GSE38832 and GSE17538). At last, the model and prognosis-associated clinical factors were used for the construction of the nomogram.\nRESULTS: Five colon cancer-related WGCNA modules (including 1160 genes) and 1153 DEGs between tumor and normal tissues were identified, inclusive of 556 overlapping DEGs. Stepwise Cox regression analyses identified there were 14 prognosis-associated DEGs, of which 12 DEGs were included in the optimized prognostic gene signature. This prognostic model presented a high forecast ability for the prognosis of colon cancer both in the TCGA training dataset and the validation datasets (GSE38832 and GSE17538; AUC > 0.8). In addition, patients' age, T classification, recurrence status, and prognostic risk score were associated with the prognosis of TCGA patients with colon cancer. The nomogram was constructed using the above factors, and the predictive 3- and 5-year survival probabilities had high compliance with the actual survival proportions.\nCONCLUSIONS: The 12-gene signature prognostic model had a high predictive ability for the prognosis of colon cancer.", "claims": [{"id": "claim-method", "statement": "The common DEGs across the TCGA, GSE44861, and GSE44076 datasets were identified using the MetaDE.ES methods in the R MetaDE package", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33441161", "locator": "sections[5] \"DEG identification by meta-analysis\" paragraph 2", "quote": "The common DEGs across the TCGA, GSE44861, and GSE44076 datasets were identified using the MetaDE.ES methods in the R MetaDE package"}], "state": "complete"}, {"id": "claim-data-access", "statement": "Besides, the RNA-seq data of colon cancer and the corresponding clinical information were downloaded from TCGA (https://gdc-portal.nci.nih.gov/). 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"2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33441161:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:09d764bed362ecd8390b40903a897724a0d4557f11fdabd7952246cc5e7d51ab", "bytes": 707, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#Tab1", "version": null, "note": "The weighted gene co-expression network analysis (WGCNA) gene modules related to colon cancer", "structure": {"pmcid": "PMC7807455", "section_index": 12, "section_title": "Extraction of WGCNA modules related to colon cancer", "row_count": 10, "column_count": 5}, "table": {"label": "Table 1", "caption": "The weighted gene co-expression network analysis (WGCNA) gene modules related to colon cancer", "rows": [["ID", "Color", "Module size", 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list of the differentially expressed genes in the optimized prognostic gene signature was identified by the Cox-proportional hazards (Cox-PH) model", "structure": {"pmcid": "PMC7807455", "section_index": 15, "section_title": "Construction of the prognostic model", "row_count": 14, "column_count": 6}, "table": {"label": "Table 2", "caption": "The list of the differentially expressed genes in the optimized prognostic gene signature was identified by the Cox-proportional hazards (Cox-PH) model", "rows": [["Symbol", "Module", "Univariate Cox regression analysis", "LASSO coefficient"], ["HR", "95%CI", "P value"], ["ADORA3", "Blue", "1.570", "1.067–2.549", "3.40E−02", "0.44262"], ["CPA3", "Blue", "0.810", "0.679–0.965", "9.50E−03", "− 0.35894"], ["CPM", "Green", "0.748", "0.561–0.995", "2.30E−02", "− 0.26349"], ["EDN3", "Green", "0.830", "0.670–1.028", "4.40E−02", "− 0.12557"], ["FCRL2", "Blue", "2.465", "1.298–4.682", "2.90E−03", "1.38523"], ["MFNG", "Blue", "1.456", "1.127–1.879", "2.00E−03", "0.35734"], ["NAT1", "Green", "0.514", "0.368–0.717", "4.55E−05", "− 0.42755"], ["PCSK5", "Green", "1.477", "1.021–2.138", "1.95E−02", "0.30206"], ["PPARGC1A", "Green", "0.579", "0.399–0.842", "2.10E−03", "− 0.34355"], ["PRRX2", "Yellow", "1.260", "1.017–1.559", "1.70E−02", "0.04376"], ["TNFRSF17", "Blue", "0.780", "0.597–0.919", "3.45E−02", "− 0.21594"], ["WDR78", "Green", "0.334", "0.158–0.707", "2.05E−03", "− 0.07166"]], "row_count": 14, "column_count": 6, "numeric_cells": 51, "header_rows": 2, "locator": "section[15]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:33441161:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7a8ac5781dd38202e6d33e3c01e05a95f55bcd936eb1d210ca1b2f5a3f5e8ee2", "bytes": 1696, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#Tab3", "version": null, "note": "Identification of the prognosis-associated factors in colon cancer (the TCGA samples) using Cox regression analysis", "structure": {"pmcid": "PMC7807455", "section_index": 17, "section_title": "Identification of prognosis-associated clinical factors", "row_count": 14, "column_count": 6}, "table": {"label": "Table 3", "caption": "Identification of the prognosis-associated factors in colon cancer (the TCGA samples) using Cox regression analysis", "rows": [["Clinical characteristics", "TCGA (N = 432)", "Univariate", "Multivariate"], ["HR (95% CI)", "p value", "HR (95% CI)", "p value"], ["Age (years, mean ± sd)", "66.78 ± 12.88", "1.018 (1.001–1.035)", "3.408E−02", "1.047 (1.021–1.073)", "3.510E−04"], ["Gender (male/female)", "230/202", "1.077 (0.719–1.610)", "7.189E−01", "–", "–"], ["Pathologic M (M0/M1/–)", "319/59/54", "4.536 (2.851–7.218)", "2.649E−12", "1.501 (0.373–6.036)", "5.671E− 01"], ["Pathologic N (N0/N1/N2)", "254/101/77", "2.088 (1.648–2.644)", "1.342E−10", "1.614 (0.839–3.103)", "1.514E−01"], ["Pathologic T(T1/T2/T3/T4)", "11/75/296/50", "2.658 (1.775–3.979)", "1.116E−06", "3.561 (1.781–7.121)", "3.280E−04"], ["Pathologic stage (I/II/III/IV/–)", "73/167/123/59/10", "2.181 (1.719–2.767)", "3.376E−11", "1.123 (0.373–3.378)", "8.362E−01"], ["Colon polyps history (yes/no/–)", "128/239/65", "0.731 (0.426–1.255)", "2.537E− 01", "–", "–"], ["Lymphatic invasion (yes/no/–)", "150/241/41", "2.150 (1.392–3.320)", "4.125E− 04", "0.922 (0.489–1.737)", "8.024E− 01"], ["Recurrence (yes/no)", "78/292/62", "2.567 (1.636–4.029)", "2.113E−05", "1.881 (1.050–3.369)", "3.363E− 02"], ["PS model status (high/low)", "216/216", "3.287 (2.082–5.189)", "4.096E−08", "2.737 (1.447–5.178)", "1.970E−03"], ["Vital status (dead/alive)", "96/336", "–", "–", "–", "–"], ["Overall survival time (months, mean ± sd)", "29.44 ± 25.43", "–", "–", "–", "–"]], "row_count": 14, "column_count": 6, "numeric_cells": 51, "header_rows": 2, "locator": "section[17]/table-wrap[1]#Tab3"}}], "gaps": ["asset:data:geo:GSE17538 not downloaded", "asset:data:geo:GSE17538 licence not read", "asset:data:geo:GSE38832 not downloaded", "asset:data:geo:GSE38832 licence not read", "asset:data:geo:GSE44076 not downloaded", "asset:data:geo:GSE44076 licence not read", "asset:data:geo:GSE44861 not downloaded", "asset:data:geo:GSE44861 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Cox regression"}}, {"id": "method-2", "family": null, "specific": null, "label": "MetaDE.ES method using the R MetaDE package", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The common DEGs across the TCGA, GSE44861, and GSE44076 datasets were identified using the MetaDE.ES methods in the R MetaDE package"}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE44861", "GSE44076", "GSE17538", "GSE38832"], "resolved_accessions": ["GSE44861", "GSE44076", "GSE17538", "GSE38832"], "statements": ["Besides, the RNA-seq data of colon cancer and the corresponding clinical information were downloaded from TCGA (https://gdc-portal.nci.nih.gov/). After sample selection, 473 samples including 432 tumor samples with clinical information and 41 normal samples were retained in this study."], "basis": "The paper names GSE44861, GSE44076, GSE17538, GSE38832 in National Center for Biotechnology Information (NCBI) gene expression omnibus (GEO) repository and the accession resolves in the repository. 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