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pmid:33569302
A prognostic nomogram for lung adenocarcinoma based on immune-infiltrating Treg-related genes: from bench to bedside.
Xiaofei Wang · Zengtuan Xiao · Jialin Gong · Zuo Liu · Mengzhe Zhang · Zhenfa Zhang
Translational lung cancer research · 2021 doi:10.21037/tlcr-20-822
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Complete file
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Therefore, we attempted to discover the possible value of Tregs for lung adenocarcinoma (LUAD).\nMETHODS: The gene-sequencing data of LUAD were applied from three Gene Expression Omnibus (GEO) datasets-GSE10072, GSE32863 and GSE43458; the corresponding fractions of tumor-infiltrating immune cells were extracted from the CIBERSORTx portal. Weighted gene coexpression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis were conducted to identify the significant module and candidate genes related to Tregs. The role of candidate genes in LUAD was further verified using data from The Cancer Genome Atlas (TCGA) database. Finally, we constructed a nomogram model to predict the prognosis of LUAD by plotting Kaplan-Meier (K-M), receiver operating characteristic (ROC) and calibration curves, which elucidated the performance of the nomogram.\nRESULTS: In total, 10,047 genes in 333 samples (196 tumor and 137 normal samples) from the GEO database were included. By WGCNA and PPI analysis, we identified a significant black module and 36 candidate genes related to Treg. Next, the candidate genes were verified using TCGA data by Cox regression analysis to screen 13 hub genes that stratified LUAD patients into low- or high-risk groups. Low-risk patients showed a significantly longer overall survival (OS) than high-risk patients (3-year OS: 70.2% vs. 35.2%; 5-year OS: 36.6% vs. 0; P=1.651E-09), and the areas under the ROC curves (AUCs) showed good (3-year AUC: 0.733; 5-year AUC: 0.777). Next, we constructed a survival nomogram combining the hub genes and clinical parameters; the low-risk patients still showed a favorable prognosis compared with that of the high-risk patients (P=7.073E-13), and the AUCs were better (3-year AUC: 0.763; 5-year AUC: 0.873).\nCONCLUSIONS: We revealed the role of immune-infiltrating Treg-related genes in LUAD and constructed a prognostic nomogram, which may help clinicians make optimal therapeutic decisions and help patients obtain better outcomes.", "claims": [{"id": "claim-method", "statement": "A Cox proportional hazards model was applied to identify survival genes related to Tregs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33569302", "locator": "sections[11] \"Statistical analysis\" paragraph 2", "quote": "A Cox proportional hazards model was applied to identify survival genes related to Tregs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The LUAD sequencing data were applied from three GEO (http://www.ncbi.nlm.nih.gov/geo/) datasets, GSE10072, GSE32863, and GSE43458.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33569302", "locator": "sections[3] \"Data source and processing\" paragraph 2", "quote": "The LUAD sequencing data were applied from three GEO (http://www.ncbi.nlm.nih.gov/geo/) datasets, GSE10072, GSE32863, and GSE43458."}], "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:33569302"], "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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"PMC7867791", "section_index": 17, "section_title": "GO and KEGG pathway enrichment analyses", "row_count": 41, "column_count": 7}, "table": {"label": "Table 2", "caption": "GO and KEGG pathway enrichment analysis of candidate genes in the most significant terms", "rows": [["Terms", "ID", "Description", "Gene ratio", "Padjust", "Gene ID", "Count"], ["Biological process", "GO:0000280", "Nuclear division", "15/35", "4.15E-14", "CENPF/TPX2/UBE2C/KIF11/CDC20/CENPE/TOP2A/ASPM/TRIP13/NUSAP1/PRC1/KNTC1/AURKA/TTK/CCNB1", "15"], ["GO:0048285", "Organelle fission", "15/35", "8.22E-14", "CENPF/TPX2/UBE2C/KIF11/CDC20/CENPE/TOP2A/ASPM/TRIP13/NUSAP1/PRC1/KNTC1/AURKA/TTK/CCNB1", "15"], ["GO:0140014", "Mitotic nuclear division", "13/35", "8.22E-14", "CENPF/TPX2/UBE2C/KIF11/CDC20/CENPE/TRIP13/NUSAP1/PRC1/KNTC1/AURKA/TTK/CCNB1", "13"], ["GO:0007088", "Regulation of mitotic nuclear division", "11/35", "6.79E-13", "CENPF/UBE2C/KIF11/CDC20/CENPE/TRIP13/NUSAP1/KNTC1/AURKA/TTK/CCNB1", "11"], ["GO:0051783", "Regulation of nuclear division", "11/35", "2.50E-12", "CENPF/UBE2C/KIF11/CDC20/CENPE/TRIP13/NUSAP1/KNTC1/AURKA/TTK/CCNB1", "11"], ["GO:0007051", "Spindle organization", "10/35", "2.06E-11", "TPX2/KIF11/CDC20/CENPE/ASPM/STIL/PRC1/AURKA/TTK/CCNB1", "10"], ["GO:1902850", "Microtubule cytoskeleton organization involved in mitosis", "9/35", "1.01E-10", "TPX2/KIF11/CDC20/CENPE/STIL/NUSAP1/PRC1/TTK/CCNB1", "9"], ["GO:0007059", "Chromosome segregation", "11/35", "2.72E-10", "CENPF/ECT2/CDC20/CENPE/TOP2A/BUB1/TRIP13/NUSAP1/PRC1/TTK/CCNB1", "11"], ["GO:0051983", "Regulation of chromosome segregation", "8/35", "6.96E-10", "CENPF/ECT2/CDC20/CENPE/BUB1/TRIP13/TTK/CCNB1", "8"], ["GO:0098813", "Nuclear chromosome segregation", "10/35", "6.96E-10", "CENPF/ECT2/CDC20/CENPE/BUB1/TRIP13/NUSAP1/PRC1/TTK/CCNB1", "10"], ["Cellular component", "GO:0005819", "Spindle", "13/35", "8.73E-13", "CENPF/ECT2/TPX2/KIF11/CDC20/CENPE/KIF20A/ASPM/PRC1/KNTC1/AURKA/TTK/CCNB1", "13"], ["GO:0000922", "Spindle pole", "9/35", "2.76E-10", "CENPF/TPX2/KIF11/CDC20/ASPM/PRC1/KNTC1/AURKA/CCNB1", "9"], ["GO:0030496", "Midbody", "8/35", "2.02E-08", "CENPF/ECT2/CENPE/CEP55/KIF20A/ASPM/PRC1/AURKA", "8"], ["GO:0098687", "Chromosomal region", "9/35", "1.62E-07", "CENPF/CENPE/BUB1/MCM4/MCM6/MCM2/KNTC1/TTK/CCNB1", "9"], ["GO:0072686", "Mitotic spindle", "6/35", "3.66E-07", "ECT2/TPX2/KIF11/CENPE/ASPM/AURKA", "6"], ["GO:0005876", "Spindle microtubule", "5/35", "5.84E-07", "KIF11/CENPE/PRC1/KNTC1/AURKA", "5"], ["GO:0000776", "Kinetochore", "6/35", "1.48E-06", "CENPF/CENPE/BUB1/KNTC1/TTK/CCNB1", "6"], ["GO:0005813", "Centrosome", "9/35", "1.48E-06", "CCNB2/CENPF/CDC20/CEP55/ASPM/STIL/AURKA/HMMR/CCNB1", "9"], ["GO:0042555", "MCM complex", "3/35", "7.85E-06", "MCM4/MCM6/MCM2", "3"], ["GO:0000775", "Chromosome, centromeric region", "6/35", "7.85E-06", "CENPF/CENPE/BUB1/KNTC1/TTK/CCNB1", "6"], ["Molecular function", "GO:0004674", "Protein serine/threonine kinase activity", "6/35", "9.86E-03", "BUB1/AURKA/CDK4/MELK/TTK/PBK", "6"], ["GO:0008094", "DNA-dependent ATPase activity", "3/35", "2.04E-02", "TOP2A/MCM4/MCM6", "3"], ["GO:0016538", "Cyclin-dependent protein serine/threonine kinase regulator activity", "2/35", "2.04E-02", "CDK4/CCNB1", "2"], ["GO:0003697", "Single-stranded DNA binding", "3/35", "2.07E-02", "RAD51AP1/MCM4/MCM6", "3"], ["GO:0004003", "ATP-dependent DNA helicase activity", "2/35", "3.66E-02", "MCM4/MCM6", "2"], ["GO:0004386", "Helicase activity", "3/35", "3.80E-02", "MCM4/MCM6/MCM2", "3"], ["GO:0004712", "Protein serine/threonine/tyrosine kinase activity", "2/35", "4.11E-02", "AURKA/TTK", "2"], ["GO:0003678", "DNA helicase activity", "2/35", "4.11E-02", "MCM4/MCM6", "2"], ["GO:0140097", "Catalytic activity, acting on DNA", "3/35", "4.11E-02", "TOP2A/MCM4/MCM6", "3"], ["GO:0008026", "ATP-dependent helicase activity", "2/35", "4.62E-02", "MCM4/MCM6", "2"], ["KEGG pathways", "hsa04110", "Cell cycle", "10/17", "9.47E-15", "CCNB2/CDC20/BUB1/PTTG1/MCM4/MCM6/MCM2/CDK4/TTK/CCNB1", "10"], ["hsa04114", "Oocyte meiosis", "6/17", "1.56E-07", "CCNB2/CDC20/BUB1/PTTG1/AURKA/CCNB1", "6"], ["hsa04914", "Progesterone-mediated oocyte maturation", "4/17", "4.57E-05", "CCNB2/BUB1/AURKA/CCNB1", "4"], ["hsa03030", "DNA replication", "3/17", "5.39E-05", "MCM4/MCM6/MCM2", "3"], ["hsa04115", "p53 signaling pathway", "3/17", "4.47E-04", "CCNB2/CDK4/CCNB1", "3"], ["hsa05166", "Human T-cell leukemia virus 1 infection", "4/17", "9.68E-04", "CCNB2/CDC20/PTTG1/CDK4", "4"], ["hsa04218", "Cellular senescence", "3/17", "4.00E-03", "CCNB2/CDK4/CCNB1", "3"], ["hsa04068", "FoxO signaling pathway", "2/17", "3.06E-02", "CCNB2/CCNB1", "2"], ["hsa04120", "Ubiquitin mediated proteolysis", "2/17", "3.46E-02", "UBE2C/CDC20", "2"], ["hsa00670", "One carbon pool by folate", "1/17", "4.15E-02", "TYMS", "1"]], "row_count": 41, "column_count": 7, "numeric_cells": 183, "header_rows": 1, "locator": "section[17]/table-wrap[1]#t2"}}], "gaps": 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