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pmid:31417870
A Robust 8-Gene Prognostic Signature for Early-Stage Non-small Cell Lung Cancer.
Ru He · Shuguang Zuo
Frontiers in oncology · 2019 doi:10.3389/fonc.2019.00693
Paper
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Experiment
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Data
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Analysis
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Complete file
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Method: In the present study, a comprehensive genome-wide profiling analysis was conducted using a retrospective pool of early-stage NSCLC patient data from the previous datasets of Gene Expression Omnibus (GEO) including GSE31210, GSE37745, and GSE50081 and The Cancer Genome Atlas (TCGA). Cox proportional hazards models were implemented to determine the association between gene expression levels and overall patient survival in each dataset. The common genes among all datasets were selected as candidate prognostic genes. A risk score model was developed and validated using four independent datasets and the entire cohort. The Kaplan-Meier with log-rank test was used to assess survival difference. Results: A univariate Cox proportional hazards regression analysis for each dataset showed that a total of 2280 genes in GSE31210, 762 genes in GSE37745, 871 genes in GSE50081, and 666 genes in TCGA were identified as candidate protective genes, while overall 2131 genes in GSE31210, 913 in GSE37745, 1107 in GSE50081, and 997 in TCGA were identified as candidate risky genes. There were 8 common genes associated with overall survival, including 7 mRNA and 1 lncRNA. By using the Step-wise multivariate Cox analysis, an 8-gene prognostic signature (CDCP1, HMMR, TPX2, CIRBP, HLF, KBTBD7, SEC24B-AS1, and SH2B1) for early-stage NSCLC was developed. Patients in the high-risk group had shorter overall survival than those in the low-risk group. Multivariate regression and stratified analysis suggested that the prognostic power of the 8-gene signature was independent of other clinical factors. Furthermore, the 8-gene signature achieved AUC values of 0.726, 0.701, 0.725 and 0.650 in GSE31210, GSE37745, GSE50081 and TCGA, respectively. Moreover, the combination of the 8-gene signature and the stage resulted to a better patient classification for survival prediction and treatment decision. Conclusion: This study developed a robust gene signature with great value for prognostic prediction in early-stage NSCLC, which may contribute to patient classification and personalized treatment decisions.", "claims": [{"id": "claim-method", "statement": "A univariate Cox proportional hazard regression model was used to assess the association of gene expression with the overall survival of NSCLC patients in each cohort. 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patients in 4 independent datasets.", "structure": {"pmcid": "PMC6684755", "section_index": 9, "section_title": "The 8-Gene Prognostic Signature Is Independent of Other Clinicopathological Factors", "row_count": 40, "column_count": 7}, "table": {"label": "Table 3", "caption": "Univariate and multivariate Cox regression analyses of the gene signature and overall survival of NSCLC patients in 4 independent datasets.", "rows": [["Variables", "Patients (N)", "Univariate analysis", "Multivariate analysis"], ["", "", "", "HR (95% CI)", "P", "HR (95% CI)", "P"], ["GSE31210"], ["Age", "< = 65/>65", "176/50", "2.58 (1.31–5.08)", "6.00E-03", "2.71 (1.31–5.63)", "7.50E-03"], ["Gender", "Male/Female", "121/105", "1.52 (0.78–2.96)", "2.20E-01", "", ""], ["ALK fusion", "−/+", "215/11", "1.49 (0.36–6.24)", "5.80E-01", "", ""], ["EGFR mutation", "−/+", "99/127", "0.47 (0.24–0.93)", "3.00E-02", "0.77 (0.36–1.67)", "5.10E-01"], ["KRAS mutation", "−/+", "206/20", "0.87 (0.27–2.85)", "8.20E-01", "", ""], ["Myc", "Low/High", "207/17", "0.70 (0.17–2.90)", "6.20E-01", "", ""], ["Stage", "IA/IB", "114/54", "2.47 (0.95–6.40)", "6.30E-02", "1.69 (0.64–4.46)", "2.90E-01"], ["Stage", "IA/II", "114/58", "6.18 (2.68–14.26)", "1.90E-05", "4.89 (2.00–11.95)", "4.90E-04"], ["Smoking", "No/Yes", "115/111", "1.64 (0.84–3.20)", "1.50E-01", "", ""], ["Risk score", "Low/High", "113/113", "4.74 (2.07–10.87)", "2.40E-04", "3.51 (1.47–8.37)", "4.60E-03"], ["GSE37745"], ["Age", "< = 65/>65", "82/83", "1.51 (1.05–2.18)", "2.60E-02", "1.46 (1.00–2.13)", "4.80E-02"], ["Gender", "Male/Female", "74/91", "1.11 (0.77–1.60)", "5.90E-01", "", ""], ["Stage", "IA/IB", "40/90", "1.71 (1.07–2.73)", "2.50E-02", "1.69 (1.04–2.72)", "3.30E-02"], ["Stage", "IA/II", "40/35", "1.77 (1.02–3.06)", "4.30E-02", "1.81 (1.01–3.23)", "4.50E-02"], ["Histological type", "Adeno/Large", "89/21", "0.97 (0.54–1.73)", "9.10E-01", "", ""], ["Histological type", "Adeno/Squamous", "89/55", "1.25 (0.84–1.85)", "2.80E-01", "", ""], ["Performance status", "0/1", "87/66", "2.04 (1.39–2.98)", "2.40E-04", "2.26 (1.53–3.34)", "4.10E-05"], ["Performance status", "0/2–3", "87/12", "1.50 (0.74–3.04)", "2.60E-01", "1.47 (0.70–3.08)", "3.10E-01"], ["Risk score", "Low/High", "83/82", "2.23 (1.54–3.23)", "2.00E-05", "2.69 (1.82–3.97)", "6.00E-07"], ["GSE50081"], ["Age", "< = 65/>65", "59/122", "1.56 (0.93–2.61)", "9.00E-02", "1.30 (0.74–2.30)", "3.60E-01"], ["Gender", "Male/Female", "83/98", "1.93 (1.19–3.14)", "7.80E-03", "1.73 (0.99–3.00)", "5.30E-02"], ["Stage", "IA/IB", "48/79", "1.76 (0.93–3.34)", "8.20E-02", "1.78 (0.83–3.83)", "1.40E-01"], ["Stage", "IA/II", "48/54", "2.46 (1.27–4.78)", "7.80E-03", "3.13 (1.39–7.01)", "5.70E-03"], ["Histological type", "Adeno/Large", "127/7", "1.71 (0.62–4.74)", "3.00E-01", "", ""], ["Histological type", "Adeno/Other", "127/4", "1.84 (0.57–5.92)", "3.00E-01", "", ""], ["Histological type", "Adeno/Squamous", "127/43", "0.8 (0.46–1.39)", "4.30E-01", "", ""], ["Smoking", "No/Yes", "24/136", "1.39 (0.66–2.92)", "3.90E-01", "", ""], ["Risk score", "Low/High", "91/90", "2.33 (1.45–3.75)", "4.90E-04", "1.92 (1.10–3.37)", "2.20E-02"], ["TCGA"], ["Age", "< = 65/>65", "325/434", "1.29 (0.95–1.75)", "1.10E-01", "", ""], ["Gender", "Male/Female", "306/453", "0.96 (0.71–1.29)", "7.70E-01", "", ""], ["Stage", "IA/IB", "213/277", "1.31 (0.87–1.97)", "1.90E-01", "1.23 (0.82–1.85)", "3.20E-01"], ["Stage", "IA/II", "213/269", "2.04 (1.36–3.05)", "5.30E-04", "1.94 (1.28–2.92)", "1.60E-03"], ["Histological type", "Adeno/Squamous", "372/387", "1.18 (0.88–1.60)", "2.70E-01", "", ""], ["Risk score", "Low/High", "380/379", "1.59 (1.18–2.14)", "2.50E-03", "1.47 (1.08–2.00)", "1.40E-02"]], "row_count": 40, "column_count": 7, "numeric_cells": 151, "header_rows": 2, "locator": "section[9]/table-wrap[1]#T3"}}, {"id": "asset:table:pmid:31417870:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:88b0f3dca7c36ca1f1f56ede060a4ff5d5d830fbd72272618372c047721a5ae6", "bytes": 1114, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[2]#T4", "version": null, "note": "Univariate and multivariate Cox regression analyses of the gene signature and overall survival of NSCLC patients in entire cohort.", "structure": {"pmcid": "PMC6684755", "section_index": 9, "section_title": "The 8-Gene Prognostic Signature Is Independent of Other Clinicopathological Factors", "row_count": 9, "column_count": 7}, "table": {"label": "Table 4", "caption": "Univariate and multivariate Cox regression analyses of the gene signature and overall survival of NSCLC patients in entire cohort.", "rows": [["Variables", "Patients (N)", "Univariate analysis", "Multivariate analysis"], ["", "", "", "HR (95% CI)", "P", "HR (95% CI)", "P"], ["Age", "< = 65/>65", "646/693", "1.85 (1.51–2.25)", "1.40E-09", "1.77 (1.44–2.17)", "4.00E-08"], ["Gender", "Male/Female", "591/749", "1.34 (1.10–1.63)", "3.90E-03", "1.11 (0.91–1.37)", "3.00E-01"], ["Stage", "I/II", "923/417", "1.75 (1.43–2.14)", "5.80E-08", "1.62 (1.32–1.99)", "3.80E-06"], ["Histological type", "Adeno/Large", "819/28", "1.61 (1.00–2.62)", "5.20E-02", "1.53 (0.94–2.49)", "8.70E-02"], ["Histological type", "Adeno/Other", "819/4", "2.10 (0.67–6.57)", "2.00E-01", "1.83 (0.58–5.76)", "3.00E-01"], ["Histological type", "Adeno/Squamous", "819/489", "1.76 (1.44–2.15)", "3.00E-08", "1.33 (1.08–1.64)", "7.80E-03"], ["Risk score", "Low/High", "671/669", "2.07 (1.69–2.53)", "1.60E-12", "1.90 (1.55–2.33)", "8.70E-10"]], "row_count": 9, "column_count": 7, "numeric_cells": 38, "header_rows": 2, "locator": "section[9]/table-wrap[2]#T4"}}], "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", "asset:data:geo:GSE50081 not downloaded", "asset:data:geo:GSE50081 licence not read"]}, "analysis": {"state": "complete", "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": 1.0, "band": "reordered", "quote": "A univariate Cox proportional hazard regression model was used to assess the association of gene expression with the overall survival of NSCLC patients in each cohort. The raw data of gene expression and corresponding clinical information of patients with early-stage NSCLC were downloaded from GEO and TCGA, respectively."}}, {"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": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"id": "method-3", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "log-rank"}}], "targets": [], "gaps": []}, "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. 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