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pmid:39702336
The role of m6A methylation genes in predicting poor prognosis in sepsis: identifying key biomarkers and therapeutic targets.
Shaokang Wang · Siye Shen · Na Cheng · Wenjun Zhou · Weili Yu · Daiyun Liang · Lijun Cao · Pinjie Zhang · Zhonghua Lu · Yun Sun
European journal of medical research · 2024 doi:10.1186/s40001-024-02194-8
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Experiment
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Complete file
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By analyzing gene expression omnibus (GEO) data set, our team explored the relationship between m6A methylation gene and poor prognosis of sepsis. The purpose of this present study is to examine new detection markers for patients with poor prognosis, provide theoretical basis for timely intervention and improve the survival rate of patients. First, GSE54514 transcriptome data were extracted from the GEO database 31 patients with sepsis related death and 72 sepsis survivors. Key genes were screened from differentially expressed genes (DEGs), least absolute shrinkage and selection operator (LSAAO) and random forest (RF). And then, METTL3, WTAP and RBM15 were further verified by quantitative reverse transcription PCR (qRT-PCR). The constructed nomogram model showed high accuracy in predicting death. These three genes are mainly involved in chemokine signaling pathway, differentiation of monocytes and T cells, and phagocytosis of immune cells. The analysis showed that a high m6A score subtype is linked to lower immunosuppression and higher survival rates in clinical samples, suggesting better immune responses and outcomes for these patients. Finally, the protective effect of METTL3 in sepsis was demonstrated in mouse sepsis model applied with METTL3 inhibitor, by conducting cell flow cytometry analysis, enzyme-linked immunosorbent assay (ELISA) and hematoxylin-eosin (HE) staining. 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The constructed nomogram model sh"], "order_basis": "paper_text_order:943", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["fect of METTL3 in sepsis was demonstrated in mouse sepsis model applied with METTL3 inhibitor,", "regulatory factors, for validation. Fifteen mice were divided into three groups: normal control gr", "ed to evaluate pro-inflammatory cytokines in mouse lung tissue. Treatment of groups: The CLP +", "antibodies used included: PE-conjugated anti-mouse IL-17A, BV421-conjugated anti-mouse CD4, Per"], "order_basis": "paper_text_order:1485", "id": "assay:2"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ed with METTL3 inhibitor, by conducting cell flow cytometry analysis, enzyme-linked immunosorbent assay", "TM2457 + sepsis model group (CLP + STM2457). Flow cytometry, enzyme-linked immunosorbent assay (ELISA),", "stablishment, tissue samples were collected. Flow cytometry: Cells were isolated from spleen tissue by g"], "order_basis": "paper_text_order:1554", "id": "assay:3"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["analysis, enzyme-linked immunosorbent assay (ELISA) and hematoxylin-eosin (HE) staining. In con", "by conducting cell flow cytometry analysis, enzyme-linked immunosorbent assay (ELISA) and hematoxylin-eosin (HE) staining.", "ytometry, enzyme-linked immunosorbent assay (ELISA), and HE staining were used to evaluate pro-", "to assess specific immune cell infiltration. ELISA: Blood was collected from the orbital area a"], "order_basis": "paper_text_order:1580", "id": "assay:4"}, {"role": "analysis", "definition_id": "principal_component_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pca_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Three feature selection algorithms—SVM–RFE [17], LASSO logistic regression [18], and RF algorithm [19]—were used to screen sepsis survival-related biomarkers."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}