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pmid:34430609
Evaluation of the roles and regulatory mechanisms of PD-1 target molecules in NSCLC progression.
Yun-Qiang Zhang · Ye Yuan · Jun Zhang · Cheng-Yi Lin · Jia-Long Guo · Hua-Song Liu · Qiang Guo
Annals of translational medicine · 2021 doi:10.21037/atm-21-2963
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Complete file
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The role of PD-1 targets in the progression of NSCLC has not been fully revealed.\nMETHODS: The differentially expressed genes (DEGs) in patients' blood after NSCLC treatment with PD-1 blocker nivolumab in the GSE141479 dataset were analyzed by GEO2R and identified in the TCGA database. The mechanism of action involved in the PD-1 target molecules via the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein-protein interaction (PPI) network shows the relationship between PD-1 target molecules. The factors affecting the prognosis of NSCLC patients were identified via the COX regression analysis and survival analysis to build the risk model and nomogram.\nRESULTS: There were 64 DEGs in patients' blood after nivolumab treatment and 48 DEGs in NSCLC tissues. The PD-1 target molecules involved cell proliferation, DNA replication, cell cycle, lung cancer, and other cellular processes. The prognostic factors CCNA2, CHEK1, DLGAP5, E2F8, FOXM1, HIST1H2BH, HJURP, MKI67, PLK1, TPX2, and TYMS, and the independent factors HIST1H2BH and PLK1, influenced the prognosis of NSCLC patients. HIST1H2BH and PLK1 were overexpressed in LUAD and LUSC tissues. The elevated expression levels of HIST1H2BH and PLK1 were related to the overall survival (OS) and the progression-free survival of NSCLC patients. High-risk NSCLC patients had a poor prognosis and were an independent factor influencing the poor prognosis of NSCLC patients. The high-risk model group was enriched with signaling mechanisms such as cell cycle, DNA replication, and homologous recombination.\nCONCLUSIONS: The risk model based on PD-1 target molecules was helpful to assess the prognosis of NSCLC patients. HIST1H2BH and PLK1 might become prognostic biomarkers of NSCLC patients.", "claims": [{"id": "claim-method", "statement": "K-M survival analysis showed that high-risk NSCLC patients in the risk model had poor prognoses (Figure 9A).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34430609", "locator": "sections[21] \"Evaluation of the risk model in the prognosis of NSCLC patients\" paragraph 2", "quote": "K-M survival analysis showed that high-risk NSCLC patients in the risk model had poor prognoses (Figure 9A)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE141479 dataset of the Gene Expression Omnibus [GEO (http://www.ncbi.nlm.nih.gov/geo/)] database contained gene expression data from the blood samples of 74 NSCLC patients. 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"note": "The expression level of PD-1 target molecules in GSE141479 NSCLC blood samples", "structure": {"pmcid": "PMC8350711", "section_index": 16, "section_title": "The expression levels of PD-1 target molecules in NSCLC", "row_count": 65, "column_count": 3}, "table": {"label": "Table 1", "caption": "The expression level of PD-1 target molecules in GSE141479 NSCLC blood samples", "rows": [["Gene", "P", "logFC"], ["SNORD111", "0.00493817", "0.72559394"], ["RNU6-948P", "0.03444443", "0.69960397"], ["KCNQ1OT1_5", "0.00166819", "0.68030422"], ["LEF1-AS1", "0.03273117", "0.65527865"], ["SNORD63", "0.00920666", "0.64174079"], ["GPRASP1", "0.00110561", "0.63013588"], ["HMGB3P4", "0.00121729", "0.61194145"], ["MTCO1P31", "0.02050908", "0.60380088"], ["ARHGAP17", "0.0023222", "0.603064"], ["CUBN", "0.01017528", "0.59152504"], ["TRAJ14", "0.002776", "0.58637359"], ["CDCA2", "0.01072148", "−0.59144421"], ["FAM83D", "0.00157576", "−0.59256397"], ["FOXM1", "0.01552184", "−0.59382417"], ["H2BFS", 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"section_title": "Construction of PD-1 target molecular risk model", "row_count": 3, "column_count": 6}, "table": {"label": "Table 5", "caption": "The independent prognostic factors of NSCLC patients", "rows": [["Gene", "coef", "HR", "HR.95L", "HR.95H", "P"], ["HIST1H2BH", "−0.220239949", "0.802326258", "0.729774307", "0.882091103", "5.25E-06"], ["PLK1", "0.303398284", "1.354453815", "1.199191723", "1.529818043", "1.04E-06"]], "row_count": 3, "column_count": 6, "numeric_cells": 12, "header_rows": 1, "locator": "section[19]/table-wrap[2]#t5"}}, {"id": "asset:table:pmid:34430609:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:001b05e6b8c81c16c0b6330baa20e6eedfa5462362b69cb653a7da872dea8d52", "bytes": 2043, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[20]/table-wrap[1]#t6", "version": null, "note": "The value of risk model factors in LUAD", "structure": {"pmcid": "PMC8350711", "section_index": 20, "section_title": "The value of risk model factors was verified in NSCLC", "row_count": 33, "column_count": 4}, "table": {"label": "Table 6", "caption": "The value of risk model factors in LUAD", "rows": [["Clinical features", "Type", "HIST1H2BH", "PLK1"], ["Gender", "Male vs. female", "4.84E-03", "1.47E-02"], ["Age", "Age (21–40 years) vs. age (81–100 years)", "1.59E-02", "NS"], ["", "Age (41–60 years) vs. age (61–80 years)", "NS", "1.91E-02"], ["", "Age (41–60 years) vs. age (81–100 years)", "1.04E-04", "NS"], ["", "Age (61–80 years) vs. age (81–100 years)", "4.98E-03", "NS"], ["Smoking", "Non smoker vs. smoker", "4.77E-04", "1.89E-05"], ["", "Non smoker vs. reformed smoker2", "4.60E-03", "1.86E-03"], ["", "Smoker vs. reformed smoker1", "3.08E-03", "2.84E-08"], ["", "Reformed smoker1 vs. reformed smoker2", "2.58E-02", "1.50E-06"], ["Clinical stage", "Stage1 vs. Stage3", "NS", "4.15E-02"], ["", "Stage1 vs. Stage4", "NS", 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"column_count": 4, "numeric_cells": 20, "header_rows": 1, "locator": "section[20]/table-wrap[2]#t7"}}, {"id": "asset:table:pmid:34430609:8", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0c0a44f19a3d2d66a552b0f5b5eb7bec98858f426b3cc4300d8a288e28b82f64", "bytes": 2373, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[22]/table-wrap[1]#t8", "version": null, "note": "The signaling mechanisms involved in the high-risk group", "structure": {"pmcid": "PMC8350711", "section_index": 22, "section_title": "The signaling mechanisms involved in the risk model", "row_count": 40, "column_count": 4}, "table": {"label": "Table 8", "caption": "The signaling mechanisms involved in the high-risk group", "rows": [["Name", "Size", "NES", "NOM P"], ["CELL_CYCLE", "124", "2.3562934", "0"], ["MISMATCH_REPAIR", "23", "2.2620559", "0"], 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["RNA_DEGRADATION", "57", "1.7536411", "0.008"], ["SPLICEOSOME", "126", "1.7790519", "0.008064516"], ["GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM", "16", "1.7177893", "0.011904762"], ["BLADDER_CANCER", "42", "1.5846695", "0.016194332"], ["PATHWAYS_IN_CANCER", "325", "1.5147824", "0.016666668"], ["GLIOMA", "65", "1.6071352", "0.018108651"], ["CITRATE_CYCLE_TCA_CYCLE", "30", "1.7157203", "0.025590552"], ["DEGRADATION", "44", "1.6497922", "0.026859503"], ["PURINE_METABOLISM", "156", "1.5934625", "0.027139874"], ["GAP_JUNCTION", "89", "1.5358167", "0.027600849"], ["PROSTATE_CANCER", "89", "1.5185701", "0.030120483"], ["DRUG_METABOLISM_OTHER_ENZYMES", "51", "1.5393608", "0.031067962"], ["THYROID_CANCER", "29", "1.5549417", "0.032467533"], ["SMALL_CELL_LUNG_CANCER", "84", "1.5911384", "0.034836065"], ["FRUCTOSE_AND_MANNOSE_METABOLISM", "32", "1.5649511", "0.035363458"], ["NON_SMALL_CELL_LUNG_CANCER", "54", "1.5211327", "0.036885247"], ["CYSTEINE_AND_METHIONINE_METABOLISM", "34", "1.4945567", 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