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pmid:35865012
Apoptosis-Related Gene-Mediated Cell Death Pattern Induces Immunosuppression and Immunotherapy Resistance in Gastric Cancer.
Xiaolu Yuan · Jun Zhou · Liping Zhou · Zudong Huang · Weiwei Wang · Jiasheng Qiu · Qiangbang Yang · Chaohao Zhang · MingHui Ma
Frontiers in genetics · 2022 doi:10.3389/fgene.2022.921163
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Experiment
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Complete file
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However, relationships between apoptosis, immunosuppression, and immunotherapy resistance of gastric cancer (GC) remain unclear. Methods: Gene expression data and matching clinical information were extracted from TCGA-STAD, GSE84437, GSE34942, GSE15459, GSE57303, ACRG/GSE62254, GSE29272, GSE26253, and IMvigor210 datasets. A consensus clustering analysis based on six apoptosis-related genes (ARGs) was performed to determine the molecular subtypes, and then an apoptosisScore was constructed based on differentially expressed and prognostic genes between molecular subtypes. Estimate R package was utilized to calculate the tumor microenvironment condition. Kaplan-Meier analysis and ROC curves were performed to further confirm the apoptosisScore efficacy. Results: Based on six ARGs, two molecular subgroups with significantly distinct survival and immune cell infiltration were identified. Then, an apoptosisScore was built to quantify the apoptosis index of each GC patient. Next, we investigated the correlations between the clinical characteristics and apoptosisScore using logistic regression. Multivariate Cox analysis shows that low apoptosisScore was an independent predictor of poor overall survival in TCGA and ACRG datasets, and was associated with the higher pathological stage. Meanwhile, low apoptosisScore was associated with higher immune cell, higher ESTIMATEScore, higher immuneScore, higher stromalScore, higher immune checkpoint, and lower tumorpurity, which was consistent with the \"immunity tidal model theory\". Importantly, low apoptosisScore was sensitive to immunotherapy. In addition, GSEA indicated that several gene ontology and Kyoto Encyclopedia of Genes and Genomes items associated with apoptosis, several immune-related pathways, and JAK-STAT signal pathway were considerably enriched in the low apoptosisScore phenotype pathway. Conclusion: Our findings propose that low apoptosisScore is a prognostic biomarker, correlated with immune infiltrates, and sensitivity to immunotherapy in GC.", "claims": [{"id": "claim-method", "statement": "Kaplan-Meier analysis and ROC curves were performed to further confirm the apoptosisScore efficacy.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35865012", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Kaplan-Meier analysis and ROC curves were performed to further confirm the apoptosisScore efficacy."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35865012", "locator": "sections[22] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Low apoptosisScore is an independent adverse prognostic factor in gastric cancer and is associated with greater immune infiltration and sensitivity to immunotherapy.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Multivariate analyses showed that low apoptosisScore was a separate prognostic indicator in GC patients (ACRG cohort: HR = 2.33, 95% CI = 1.89–2.86, p < 0.001, TCGA cohort: HR = 1.33, 95% CI = 1.09–1.62, p = 0.004) (Figures 6A,B)."}, "evidence": [{"asset": "source:pmid:35865012", "locator": "sections[17] \"Prognostic Value of apoptosisScore in Gastric Cancer Patients\" paragraph 2", "quote": "Multivariate analyses showed that low apoptosisScore was a separate prognostic indicator in GC patients (ACRG cohort: HR = 2.33, 95% CI = 1.89–2.86, p < 0.001, TCGA cohort: HR = 1.33, 95% CI = 1.09–1.62, p = 0.004) (Figures 6A,B)."}, {"asset": "source:pmid:35865012", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our findings propose that low apoptosisScore is a prognostic biomarker, correlated with immune infiltrates, and sensitivity to immunotherapy in GC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Low apoptosisScore is an independent adverse prognostic factor in gastric cancer and is associated with greater immune infiltration and sensitivity to immunotherapy.", "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:35865012"], "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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