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pmid:33161837
Development and Validation of a Scoring System Based on 9 Glycolysis-Related Genes for Prognosis Prediction in Gastric Cancer.
Tianqi Luo · Yufei Du · Jinling Duan · Chengcai Liang · Guoming Chen · Kaiming Jiang · Yongming Chen · Yingbo Chen
Technology in cancer research & treatment · 2020 doi:10.1177/1533033820971670
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Experiment
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Analysis
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Complete file
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However, increasing evidences have revealed the correlation between the glycolysis process and tumorigenesis. This study is aim to develop a list of glycolysis-related genes for risk stratification in gastric cancer patients. We included 500 patients' sample data from GSE62254 and GSE26942 datasets, and classified patients into training (n = 350) and testing sets (n = 150) at a ratio of 7: 3. Univariate and multivariate Cox regression analysis were performed to screen genes having prognostic value. Based on HALLMARK gene sets, we identified 9 glycolysis-related genes (BPNT1, DCN, FUT8, GMPPA, GPC3, LDHC, ME2, PLOD2, and UGP2). On the basis of risk score developed by the 9 genes, patients were classified into high- and low-risk groups. The survival analysis showed that the high-risk patients had a worse prognosis (p < 0.001). Similar finding was observed in the testing cohort and 2 independent cohorts (GSE13861 and TCGA-STAD, all p < 0.001). The multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for overall survival (p < 0.001). Furthermore, we constructed a nomogram that integrated the risk score and tumor stage, age, and adjuvant chemotherapy. Through comparing the results of the receiver operating characteristic curves and decision curve analysis, we found that the nomogram had a superior predictive accuracy than conventional TNM staging system, suggesting that the risk score combined with other clinical factors (age, tumor stage, and adjuvant chemotherapy) can develop a robust prediction for survival and improve the individualized clinical decision making of the patient.In conclusion, we identified 9 glycolysis-related genes from hallmark glycolysis pathway. 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To determine whether the hallmark glycolysis pathway showed significant difference between GC and normal samples, we included GSE66229 dataset to perform GSEA analysis based on HALLMARK gene set. GSE66229 was composed of GSE62254 subseries and 100 case normal tissues, and the result revealed that hallmark glycolysis pathway was significantly enriched in the GC sample group (p = 0.031, FDR q < 0.25, |NES| ≥ 1; Figure 1A).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1523727", "GSM1523728", "GSM1523729", "GSM1523744", "GSM1523745", "GSM1523746", "GSM1523747", "GSM1523748", "GSM1523765", "GSM1523768", "GSM1523769", "GSM1523770", "GSM1523771", "GSM1523772", "GSM1523773", "GSM1523774", "GSM1523775", "GSM1523776", "GSM1523777", "GSM1523778", "GSM1523779", "GSM1523780", "GSM1523781", "GSM1523782", "GSM1523783", "GSM1523784", "GSM1523785", "GSM1523786", "GSM1523787", "GSM1523788", "GSM1523789", "GSM1523790", "GSM1523791", "GSM1523792", "GSM1523793", "GSM1523794", "GSM1523795", "GSM1523796", "GSM1523797", "GSM1523798", "GSM1523799", "GSM1523800", "GSM1523801", "GSM1523802", "GSM1523803", "GSM1523804", "GSM1523805", "GSM1523806", "GSM1523807", "GSM1523808", "GSM1523809", "GSM1523810", "GSM1523811", "GSM1523812", "GSM1523813", "GSM1523814", "GSM1523815", "GSM1523816", "GSM1523817", "GSM1523818", "GSM1523819", "GSM1523820", "GSM1523821", "GSM1523822", "GSM1523823", "GSM1523824", "GSM1523825", "GSM1523826", "GSM1523827", "GSM1523828", "GSM1523829", "GSM1523830", "GSM1523831", "GSM1523832", "GSM1523833", "GSM1523834", "GSM1523835", "GSM1523836", "GSM1523837", "GSM1523838", "GSM1523839", "GSM1523840", "GSM1523841", "GSM1523842", "GSM1523843", "GSM1523844", "GSM1523845", "GSM1523846", "GSM1523847", "GSM1523848", "GSM1523849", "GSM1523850", "GSM1523851", "GSM1523852", "GSM1523853", "GSM1523854", "GSM1523855", "GSM1523856", "GSM1523857", "GSM1523858", "GSM1523859", "GSM1523860", "GSM1523861", "GSM1523862", "GSM1523863", "GSM1523864", "GSM1523865", "GSM1523866", "GSM1523867", "GSM1523868", "GSM1523869", "GSM1523870", "GSM1523871", "GSM1523872", "GSM1523873", "GSM1523874", "GSM1523875", "GSM1523876", "GSM1523877", "GSM1523878", "GSM1523879", "GSM1523880", "GSM1523881", "GSM1523882", "GSM1523883", "GSM1523884", "GSM1523885", "GSM1523886", "GSM1523887", "GSM1523888", "GSM1523889", "GSM1523890", "GSM1523891", "GSM1523892", "GSM1523893", "GSM1523894", "GSM1523895", "GSM1523896", "GSM1523897", "GSM1523898", "GSM1523899", "GSM1523901", "GSM1523903", "GSM1523904", "GSM1523905", "GSM1523906", "GSM1523908", "GSM1523909", "GSM1523910", "GSM1523911", "GSM1523918", "GSM1523919", "GSM1523920", "GSM1523921", "GSM1523922", "GSM1523923", "GSM1523924", "GSM1523925", "GSM1523926", "GSM1523927", "GSM1523928", "GSM1523929", "GSM1523930", "GSM1523931", "GSM1523932", "GSM1523933", "GSM1523934", "GSM1523935", "GSM1523936", "GSM1523937", "GSM1523938", "GSM1523939", "GSM1523940", "GSM1523941", "GSM1523942", "GSM1523943", "GSM1523944", "GSM1523945", "GSM1523946", "GSM1523947", "GSM1523948", "GSM1523949", "GSM1523950", "GSM1523951", "GSM1523952", "GSM1523953", "GSM1523954", "GSM1523955", "GSM1523956", "GSM1523957", "GSM1523958", "GSM1523959", "GSM1523960", "GSM1523961", "GSM1523962", "GSM1523963", "GSM1523964", "GSM1523965", "GSM1523966", "GSM1523967", "GSM1523968", "GSM1523969", "GSM1523970", "GSM1523971", "GSM1523972", "GSM1523973", "GSM1523974", "GSM1523975", "GSM1523976", "GSM1523977", "GSM1523978", "GSM1523979", "GSM1523980", "GSM1523981", "GSM1523982", "GSM1523983", "GSM1523984", "GSM1523985", "GSM1523986", "GSM1523987", "GSM1523988", "GSM1523989", "GSM1523990", "GSM1523991", "GSM1523992", "GSM1523993", "GSM1523994", "GSM1523995", "GSM1523996", "GSM1523997", "GSM1523998", "GSM1523999", "GSM1524000", "GSM1524001", "GSM1524002", "GSM1524003", "GSM1524004", "GSM1524005", "GSM1524006", "GSM1524007", "GSM1524008", "GSM1524009", "GSM1524010", "GSM1524011", "GSM1524012", "GSM1524013", "GSM1524014", "GSM1524015", "GSM1524016", "GSM1524017", "GSM1524018", "GSM1524019", "GSM1524020", "GSM1524021", "GSM1524022", "GSM1524023", "GSM1524024", "GSM1524025", "GSM1524026", "GSM1524027", "GSM1524028", "GSM1524029", "GSM1524030", "GSM1524031", "GSM1524032", "GSM1524033", "GSM1524034", "GSM1524035", "GSM1524036", "GSM1524037", "GSM1524038", "GSM1524039", "GSM1524040", "GSM1524041", "GSM1524042", "GSM1524043", "GSM1524044", "GSM1524045", "GSM1524046", "GSM1524047", "GSM1524048", "GSM1524049", "GSM1524050", "GSM1524051", "GSM1524052", "GSM1524053", "GSM1524054", "GSM1524055", "GSM1524056", "GSM1524057", "GSM1524058", "GSM1524059", "GSM1524060", "GSM1524061", "GSM1524062", "GSM1524068", "GSM1524069", "GSM1524070", "GSM1524071", "GSM1524072"], "sample_count": 300, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Molecular analysis of gastric cancer identifies discrete subtypes associated with distinct clinical characteristics and survival outcomes: the ACRG (Asian Cancer Research Group) study [gastric tumors]", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE66229", "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=GSE66229", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE66229", "version": null, "note": "First, we downloaded the microarray data of GC from the Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/) database. In addition, we merged 2 GEO datasets (GSE62254 and GSE26942) to develop model. To determine whether the hallmark glycolysis pathway showed significant difference between GC and normal samples, we included GSE66229 dataset to perform GSEA analysis based on HALLMARK gene set. GSE66229 was composed of GSE62254 subseries and 100 case normal tissues, and the result revealed that hallmark glycolysis pathway was significantly enriched in the GC sample group (p = 0.031, FDR q < 0.25, |NES| ≥ 1; Figure 1A).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "First, we downloaded the microarray data of GC from the Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/) database. In addition, we merged 2 GEO datasets (GSE62254 and GSE26942) to develop model. To determine whether the hallmark glycolysis pathway showed significant difference between GC and normal samples, we included GSE66229 dataset to perform GSEA analysis based on HALLMARK gene set. GSE66229 was composed of GSE62254 subseries and 100 case normal tissues, and the result revealed that hallmark glycolysis pathway was significantly enriched in the GC sample group (p = 0.031, FDR q < 0.25, |NES| ≥ 1; Figure 1A).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1523727", "GSM1523728", "GSM1523729", "GSM1523730", "GSM1523731", "GSM1523732", "GSM1523733", "GSM1523734", "GSM1523735", "GSM1523736", "GSM1523737", "GSM1523738", "GSM1523739", "GSM1523740", "GSM1523741", "GSM1523742", "GSM1523743", "GSM1523744", "GSM1523745", "GSM1523746", "GSM1523747", "GSM1523748", "GSM1523749", "GSM1523750", "GSM1523751", "GSM1523752", "GSM1523753", "GSM1523754", "GSM1523755", "GSM1523756", "GSM1523757", "GSM1523758", "GSM1523759", "GSM1523760", "GSM1523761", "GSM1523762", "GSM1523763", "GSM1523764", "GSM1523765", "GSM1523766", "GSM1523767", "GSM1523768", "GSM1523769", "GSM1523770", "GSM1523771", "GSM1523772", "GSM1523773", "GSM1523774", "GSM1523775", 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"GSM1523847", "GSM1523848", "GSM1523849", "GSM1523850", "GSM1523851", "GSM1523852", "GSM1523853", "GSM1523854", "GSM1523855", "GSM1523856", "GSM1523857", "GSM1523858", "GSM1523859", "GSM1523860", "GSM1523861", "GSM1523862", "GSM1523863", "GSM1523864", "GSM1523865", "GSM1523866", "GSM1523867", "GSM1523868", "GSM1523869", "GSM1523870", "GSM1523871", "GSM1523872", "GSM1523873", "GSM1523874", "GSM1523875", "GSM1523876", "GSM1523877", "GSM1523878", "GSM1523879", "GSM1523880", "GSM1523881", "GSM1523882", "GSM1523883", "GSM1523884", "GSM1523885", "GSM1523886", "GSM1523887", "GSM1523888", "GSM1523889", "GSM1523890", "GSM1523891", "GSM1523892", "GSM1523893", "GSM1523894", "GSM1523895", "GSM1523896", "GSM1523897", "GSM1523898", "GSM1523899", "GSM1523900", "GSM1523901", "GSM1523902", "GSM1523903", "GSM1523904", "GSM1523905", "GSM1523906", "GSM1523907", "GSM1523908", "GSM1523909", "GSM1523910", "GSM1523911", "GSM1523912", "GSM1523913", "GSM1523914", "GSM1523915", "GSM1523916", "GSM1523917", 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"group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Molecular analysis of gastric cancer identifies discrete subtypes associated with distinct clinical characteristics and survival outcomes: the ACRG (Asian Cancer Research Group) study", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33161837:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:286061d70c579731fb1209cd49cd489985b863ec298db1177d1c4a5d11e1ef04", "bytes": 2082, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#table1-1533033820971670", "version": null, "note": "Clinicopathological Characteristics.", "structure": {"pmcid": "PMC7658532", "section_index": 3, "section_title": "Data Collection and 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"146 (48.6)", "141 (70.5)", "19 (29.7)", "71 (21.1)"], ["Mixed", "17 (5.7)", "7 (3.5)", "12 (18.8)", "1 (0.3)"], ["Unknown", "3 (1.0)", "12 (6.0)", "4 (6.2)", "207 (61.4)"], ["Adjuvant chemotherapy", "", "", "", ""], ["No", "156 (52.0)", "94 (47.0)", "15 (23.4)", "35 (10.4)"], ["Yes", "144 (48.0)", "106 (53.0)", "49 (76.6)", "16 (4.7)"], ["Unknown", "0 (0.0)", "0 (0.0)", "0 (0.0)", "286 (84.9)"], ["Tumor location", "", "", "", ""], ["Antrum", "150 (50.0)", "109 (54.5)", "26 (40.6)", "120 (35.6)"], ["Body", "117 (39.0)", "84 (42.0)", "32 (50.0)", "121 (35.9)"], ["Cardia", "32 (10.7)", "7 (3.5)", "4 (6.2)", "84 (24.9)"], ["Unknown", "1 (0.3)", "0 (0.0)", "2 (3.2)", "12 (3.6)"], ["Histological grade", "", "", "", ""], ["G1/G2", "123 (41.0)", "0 (0.0)", "0 (0.0)", "129 (38.3)"], ["G3", "177 (59.0)", "0 (0.0)", "0 (0.0)", "199 (59.0)"], ["Unknown", "0 (0.0)", "200 (100.0)", "64 (100.0)", "9 (2.7)"], ["Overall survival", "", "", "", ""], ["Dead", "152 (50.7)", "88 (44.0)", "29 (45.3)", "142 (42.1)"], ["Alive", "148 (49.3)", "112 (56.0)", "35 (54.7)", "195 (54.9)"], ["Survival time (median)", "57.9 (17.8, 78.9)", "38.0 (14.3, 66.5)", "87.50 (32.8, 91.0)", "16.2 (9.7, 27.3)"]], "row_count": 35, "column_count": 5, "numeric_cells": 111, "header_rows": 1, "locator": "section[3]/table-wrap[1]#table1-1533033820971670"}}, {"id": "asset:table:pmid:33161837:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:76ad3ccf6ba9ffa846bfeb4f2ebb416ec9c0f9bbfa0c0417db2cd88155ae94b9", "bytes": 748, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#table2-1533033820971670", "version": null, "note": "Univariate and Multivariate Cox Regression Analyses of the Risk Score and Clinical Characteristics With the Overall Survival in the Training Set.", "structure": {"pmcid": "PMC7658532", "section_index": 9, "section_title": "Validation and Evaluation of the Signature", "row_count": 6, "column_count": 7}, "table": {"label": "Table 2.", "caption": "Univariate and Multivariate Cox Regression Analyses of the Risk Score and Clinical Characteristics With the Overall Survival in the Training Set.", "rows": [["", "Univariate analysis", "Multivariate analysis"], ["Variable", "HR", "95%CI", "p-value", "HR", "95%CI", "p-value"], ["Age", "1.02", "1.00-1.03", "0.017", "1.03", "1.01-1.04", "< 0.001"], ["Tumor stage (III/IV vs. I/II)", "2.52", "2.01-3.15", "< 0.001", "2.33", "1.87-2.90", "< 0.001"], ["Adjuvant chemotherapy (Yes vs. No)", "0.55", "0.40-0.76", "< 0.001", "0.62", "0.44-0.86", "0.004"], ["Risk score", "1.69", "1.52-1.87", "< 0.001", "1.60", "1.42-1.81", "< 0.001"]], "row_count": 6, "column_count": 7, "numeric_cells": 26, "header_rows": 2, "locator": "section[9]/table-wrap[1]#table2-1533033820971670"}}], "gaps": ["asset:data:geo:GSE13861 not downloaded", "asset:data:geo:GSE13861 licence not read", "asset:data:geo:GSE26942 not downloaded", "asset:data:geo:GSE26942 licence not read", "asset:data:geo:GSE62254 not downloaded", "asset:data:geo:GSE62254 licence not read", "asset:data:geo:GSE66229 not downloaded", "asset:data:geo:GSE66229 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": 1.0, "band": "verbatim", "quote": "Univariate and multivariate Cox regression analysis were performed to screen genes having prognostic value."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": 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