The Better Survival of MSI Subtype Is Associated With the Oxidative Stress Related Pathways in Gastric Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32850385", "kind": "science-record", "revision": 8, "content_hash": "sha256:78e7f8a91774fac004620907fbcc3cb2ea8682d970668304886f20b126647039", "created_at": "2026-11-01T15:41:08Z", "updated_at": "2026-11-01T22:45:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The Better Survival of MSI Subtype Is Associated With the Oxidative Stress Related Pathways in Gastric Cancer.", "doi": "10.3389/fonc.2020.01269", "pmid": "32850385", "authors": ["Lei Cai", "Yeqi Sun", "Kezhou Wang", "Wenbin Guan", "Juanqing Yue", "Junlei Li", "Ruifen Wang", "Lifeng Wang"], "journal": "Frontiers in oncology", "year": 2020, "abstract": "Background: Gastric cancer (GC) is the third leading fatal cancer in the world and its incidence ranked second among all malignant tumors in China. The molecular classification of GC, proposed by the The Cancer Genome Atlas (TCGA), was added to the updated edition (2019) of WHO classification for digestive system tumor. Although MSI and EBV subtypes appeared as ever-increasingly significant roles in immune checkpoint inhibitor therapy, the underlying mechanisms are still unclear. Methods: We systematically summarized the relationship between EBV, d-MMR/MSI-H subtypes and clinicopathological parameters in 271 GC cases. Furthermore, GSE62254/ACRG and TCGA-STAD datasets, originated from Gene Expression Omnibus (GEO) and TCGA respectively, were analyzed to figure out the prognosis related molecular characteristics by bioinformatics methods. Results: Patients with MSI subtype had better prognosis than the MSS subtype (P = 0.013) and considered as an independent biomarker by the univariate analysis (P = 0.017) and multivariate analysis (P = 0.050). While there was no significant difference between EBV positive and negative tissues (P = 0.533). The positive prognostic value conferred by MSI in different cohorts was revalidated via the clinical analysis of GSE62254/ACRG and TCGA-STAD datasets regardless of race. Then key gene module that tightly associated with better status and longer OS time for MSI cases was obtained from weighted gene co-expression network analysis(WGCNA). NUBP2 and ENDOG were screened from the gene cluster and oxidative phosphorylation, reactive oxygen species(ROS) and glutathione metabolism were analyzed to be the differential pathways in their highly expressed groups. Conclusions: Our results manifested the significant prognostic value of MSI in Chinese GC cohort and comparisons with other populations. More opportunities to induce apoptosis of cancer cells, led by the unbalance between antioxidant system and ROS accumulation, lay foundations for unveiling the better prognosis in MSI phenotype through the bioinformatics analysis.", "claims": [{"id": "claim-method", "statement": "The Kaplan-Meier method (and the log-rank test) as well as Cox's proportional hazards regression model were used for univariate survival analysis. Multivariate survival analysis was performed by Cox's proportional hazards regression model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32850385", "locator": "sections[11] \"Statistical Analysis\" paragraph 2", "quote": "The Kaplan-Meier method (and the log-rank test) as well as Cox's proportional hazards regression model were used for univariate survival analysis. Multivariate survival analysis was performed by Cox's proportional hazards regression model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study, these can be found in The Cancer Genome Atlas via the UCSC Xena browser (http://xena.ucsc.edu/); the NCBI Gene Expression Omnibus (GSE62254).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32850385", "locator": "sections[20] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study, these can be found in The Cancer Genome Atlas via the UCSC Xena browser (http://xena.ucsc.edu/); the NCBI Gene Expression Omnibus (GSE62254)."}], "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:32850385"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE62254"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE62254"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32850385", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2020.01269", "sha256": 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"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:32850385:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:741ec95bd71436e47803335805e95929c781637815c4d57808f120feef567f79", "bytes": 2410, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#T1", "version": null, "note": "The relationship between EBV and d-MMR/MSI-H subtypes and clinicopathological parameters in 271 gastric cancers.", "structure": {"pmcid": "PMC7399340", "section_index": 13, "section_title": "Prognosis and Potential Predictive Value of d-MMR/MSI-H Status in Different Cohorts", "row_count": 29, "column_count": 8}, "table": {"label": "Table 1", "caption": "The relationship between EBV and d-MMR/MSI-H subtypes and clinicopathological parameters in 271 gastric cancers.", "rows": [["", "", "EBV", "", "d-MMR/ MSI-H", ""], ["", "", "(+)", "(–)", "P", "(+)", "(–)", "P"], ["", "Median age", "61", "65", "", "70.5", "64", ""], ["Age (%)", ">65", "4 (44.4)", "122 (46.6)", "1.000", "19 (67.9)", "107 (44)", "0.017"], ["", "≦65", "5 (55.6)", "140 (53.4)", "", "9 (32.1)", "136 (56)", ""], ["Gender (%)", "Male", "6 (66.7)", "176 (46.4)", "1.000", "13 (46.4)", "169 (69.5)", "0.014"], ["", "Female", "3 (33.3)", "86 (53.6)", "", "15 (53.6)", "74 (30.5)", ""], ["Location (%)", "GEJ-cardia", "2 (22.2)", "27 (10.3)", "0.248", "1 (3.6)", "28 (11.5)", "0.197"], ["", "Non-GEJ-cardia", "7 (77.8)", "235 (89.7)", "", "27 (96.4)", "215 (88.5)", ""], ["Location (%)", "Antrum", "4 (44.4)", "150 (57.3)", "0.674", "20 (71.4)", "134 (55.1)", "0.099"], ["", "Non- antrum", "5 (55.6)", "112 (42.7)", "", "8 (28.6)", "109 (44.9)", ""], ["Size (%)", "<5", "3 (33.3)", "110 (28.6)", "0.862", "8 (28.6)", "105 (43.2)", "0.137"], ["", "≧5", "6 (66.7)", "152 (71.4)", "", "20 (71.4)", "138 (56.8)", ""], ["Differentiation (%)", "Well-moderate", "1 (11.1)", "45 (10.7)", "0.980", "3 (10.7)", "43 (17.7)", "0.505"], ["", "Poor", "8 (88.9)", "217 (89.3)", "", "25 (89.3)", "200 (82.3)", ""], ["Lauren (%)", "Intestinal", "3 (33.3)", "119 (45.4)", "0.707", "13 (46.4)", "109 (44.9)", "0.874"], ["", "Nonintestinal", "6 (66.7)", "143 (54.6)", "", "15 (53.6)", "134 (55.1)", ""], ["T (%)", "T1-T3", "8 (88.9)", "180 (68.7)", "0.355", "26 (92.9)", "162 (47.2)", "0.000"], ["", "T4", "1 (11.1)", "82 (31.3)", "", "2 (7.1)", "81 (52.8)", ""], ["N (%)", "N0", "4 (44.4)", "53 (20.2)", "0.181", "14 (50)", "43 (17.7)", "0.000"], ["", "N+", "5 (55.6)", "209 (79.8)", "", "14 (50)", "200 (82.3)", ""], ["M (%)", "M0", "8 (88.9)", "259 (98.9)", "0.127", "28 (100)", "239 (98.4)", "1.000"], ["", "M1", "1 (11.1)", "3 (1.1)", "", "0 (0)", "4 (1.6)", ""], ["TNM (%)", "I–II", "5 (55.6)", "97 (37)", "0.436", "19 (67.9)", "83 (34.2)", "0.000"], ["", "III–IV", "4 (44.4)", "165 (63)", "", "9 (32.1)", "160 (65.8)", ""], ["WHO (%)", "Medullary", "3 (33.3)", "3 (1.1)", "0.000", "2 (7.1)", "4 (1.6)", "0.119"], ["", "Non-medullary", "6 (66.7)", "259 (98.9)", "", "26 (92.9)", "239 (98.4)", ""], ["WHO (%)", "Papillary-tubular", "3 (33.3)", "143 (54.6)", "0.359", "19 (67.9)", "128 (52.7)", "0.127"], ["", "Non-papillary-tubular", "6 (66.7)", "119 (45.4)", "", "9 (32.1)", "115 (47.3)", ""]], "row_count": 29, "column_count": 8, "numeric_cells": 138, "header_rows": 3, "locator": "section[13]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:32850385:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e2f1abb41fb76c81ddb25c39a28496de9777ef56108f272f70b2195a5875725f", "bytes": 1504, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[2]#T2", "version": null, "note": "Univariate and multivariable analysis of overall survival in 271 gastric cancer.", "structure": {"pmcid": "PMC7399340", "section_index": 13, "section_title": "Prognosis and Potential Predictive Value of d-MMR/MSI-H Status in Different Cohorts", "row_count": 15, "column_count": 8}, "table": {"label": "Table 2", "caption": "Univariate and multivariable analysis of overall survival in 271 gastric cancer.", "rows": [["", "Univariate analysis", "Multivariable analysis"], ["", "P (log-rank test)", "P (Cox's test)", "HR", "95% CI", "P (Cox's test)", "HR", "95% CI"], ["d-MMR/MSI-H status (Yes vs. No)", "0.013", "0.017", "2.73", "1.20–6.23", "0.050", "2.33", "1.00–5.43"], ["EBV (+ vs. –)", "0.533", "0.534", "0.75", "0.31–1.85", "", "", ""], ["Age", "0.000", "0.003", "1.03", "1.01–1.05", "0.000", "1.04", "1.02–1.06"], ["Sex (male vs. female)", "0.092", "0.093", "1.39", "0.95–2.95", "", "", ""], ["Location (antrum vs. nonantrum)", "0.424", "0.422", "0.86", "0.59–1.25", "", "", ""], ["Size (<5 vs. ≧5)", "0.078", "0.080", "1.41", "0.96–2.07", "", "", ""], ["Differentiation (well-moderate vs. poor)", "0.226", "0.228", "1.39", "0.82–2.35", "", "", ""], ["Lauren (intestinal vs. nonintestinal)", "0.003", "0.004", "1.78", "1.20–2.64", "0.302", "1.31", "0.78–2.21"], ["WHO (poorly cohesive components vs. remant)", "0.000", "0.000", "2.04", "1.40–2.97", "0.130", "1.48", "0.89–2.46"], ["pT stage (T1 + T2 vs. T3 + T4)", "0.000", "0.000", "2.61", "1.79–3.81", "0.065", "2.44", "0.95–6.32"], ["pN stage (N0 vs. N+)", "0.002", "0.003", "2.35", "1.34–4.12", "0.360", "0.65", "0.26–1.63"], ["M stage (M0 vs. M1)", "0.467", "0.476", "0.49", "0.07–3.51", "", "", ""], ["TNM (I + II vs. III + IV)", "0.000", "0.000", "3.86", "2.39–6.23", "0.003", "3.47", "1.55–7.77"]], "row_count": 15, "column_count": 8, "numeric_cells": 76, "header_rows": 2, "locator": "section[13]/table-wrap[2]#T2"}}, {"id": "asset:table:pmid:32850385:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:054e6d4bb461c466c077169f2d387c4d2aa0cd6af29fbb384a4cc4cea7f55b2b", "bytes": 1514, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[3]#T3", "version": null, "note": "The relationship between MSI subtype and clinicopathological parameters in 309 gastric cancers in TCGA.", "structure": {"pmcid": "PMC7399340", "section_index": 13, "section_title": "Prognosis and Potential Predictive Value of d-MMR/MSI-H Status in Different Cohorts", "row_count": 30, "column_count": 5}, "table": {"label": "Table 3", "caption": "The relationship between MSI subtype and clinicopathological parameters in 309 gastric cancers in TCGA.", "rows": [["", "d-MMR/MSI-H"], ["", "", "(–)", "(+)", "P"], ["Number", "", "259", "50", ""], ["Median age"], ["Age (%)", "≤ 65", "124 (47.9)", "14 (28.0)", "0.015"], ["", ">65", "135 (52.1)", "36 (72.0)", ""], ["Gender (%)", "Male", "177 (68.3)", "26 (52.0)", "0.039"], ["", "Female", "82 (31.7)", "24 (48.0)", ""], ["Location (%)", "Non-cardia", "188 (72.6)", "45 (90.0)", "0.015"], ["", "Cardia", "71 (27.4)", "5 (10.0)", ""], ["Location (%)", "Non-antrum", "173 (66.8)", "20 (40.0)", "0.001"], ["", "Antrum", "86 (33.2)", "30 (60.0)", ""], ["Race (%)", "NA", "32 (12.4)", "13 (26.0)", "0.068"], ["", "White", "165 (63.7)", "25 (50.0)", ""], ["", "Asian", "52 (20.1)", "11 (22.0)", ""], ["", "Black", "10 (3.9)", "1 (2.0)", ""], ["T (%)", "T1–T3", "191 (73.7)", "31 (62.0)", "0.129"], ["", "T4", "68 (26.3)", "19 (38.0)", ""], ["N (%)", "N0", "70 (27.0)", "19 (38.0)", "0.217"], ["", "N+", "185 (71.4)", "31 (62.0)", ""], ["", "NX", "4 (1.5)", "0 (0.0)", ""], ["M (%)", "M0", "227 (87.6)", "46 (92.0)", "0.564"], ["", "M1", "18 (6.9)", "3 (6.0)", ""], ["", "MX", "14 (5.4)", "1 (2.0)", ""], ["Stage (%)", "I–II", "108 (41.7)", "27 (54.0)", "0.147"], ["", "III–IV", "151 (58.3)", "23 (46.0)", ""], ["NUBP2 (%)", "Low", "184 (71.0)", "25 (50.0)", "0.006"], ["", "High", "75 (29.0)", "25 (50.0)", ""], ["ENDOG (%)", "Low", "151 (58.3)", "12 (24.0)", "<0.001"], ["", "High", "108 (41.7)", "38 (76.0)", ""]], "row_count": 30, "column_count": 5, "numeric_cells": 67, "header_rows": 2, "locator": "section[13]/table-wrap[3]#T3"}}], "gaps": ["asset:data:geo:GSE62254 not downloaded", "asset:data:geo:GSE62254 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": "verbatim", "quote": "The Kaplan-Meier method (and the log-rank test) as well as Cox's proportional hazards regression model were used for univariate survival analysis. 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