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pmid:36091333
Lipid Metabolic-Related Signature CYP19A1 is a Potential Biomarker for Prognosis and Immune Cell Infiltration in Gastric Cancer.
Nan Wang · Xuanyu Huang · Qian Long
Journal of inflammation research · 2022 doi:10.2147/JIR.S378212
Paper
complete
Experiment
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Data
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Analysis
complete
Execution
absent
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Complete file
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Our study aim to explore a novel lipid metabolism-related prognostic marker for GC.\nMethods: Transcriptional status and clinical features were obtained from the TCGA-STAD database. The differentially expressed lipid metabolic genes and the risk prognostic model were developed by using bioinformatics and Cox regression analyses. ROC and Kaplan-Meier analysis were established to assess the performance of the risk predictive score model. GSE84437 dataset was used for external validation. Immunochemistry (IHC) was used to examine the expression of CYP19A1 in GC patients. Gene Set Enrichment Analysis (GSEA) was conducted to elucidate the underlying enriched mechanisms. TIMER and CIBERSORT analysis were performed to explore the relationship between CYP19A1 and immune microenvironment.\nResults: A novel lipid metabolic gene signature (including MTTP, CYP19A1, MYB, SERPINE1), and specifically CYP19A1, might be a promising prognostic factor for GC. Using the validation cohort, ROC curves indicate a good showing of our risk model. Based on the signature yielded a significant difference OS time between the low- and high-risk groups. Cox regression indicates that the signature is an independent prognostic variable. ROC curves present better and reliability predictive accuracy. The IHC data validate that high expression of CYP19A1 was found in GC tissues. GSEA analysis reveals that higher expression of CYP19A1 may significantly up-regulate genes involved in fatty acid metabolism and glycerolipid metabolism. CIBERSORT analysis suggests that CYP19A1 is related to the infiltration of multiple immune cells.\nConclusion: CYP19A1 could be an independent prognostic factor and a novel metabolic-targeted treatment strategy for gastric cancer.", "claims": [{"id": "claim-method", "statement": "Univariate Cox analysis revealed that tumor stage, age and lipid metabolism-related signature were significantly associated with overall survival of GC patients (Figure 2F). Multivariable Cox regression analysis proved the risk score model was an independent and statistically significant for GC survival (Figure 2G).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36091333", "locator": "sections[12] \"Identification of Prognosis-Related Lipid Metabolism Genes and Establishment of a Prognostic Model\" paragraph 2", "quote": "Univariate Cox analysis revealed that tumor stage, age and lipid metabolism-related signature were significantly associated with overall survival of GC patients (Figure 2F). Multivariable Cox regression analysis proved the risk score model was an independent and statistically significant for GC survival (Figure 2G)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GC mRNA expression and clinical data were obtained from the TCGA data portal (https://portal.gdc.cancer.gov/). There were 407 patients with mRNA expression and clinical data. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE84437", "GSE54129"], "resolved_accessions": ["GSE84437", "GSE54129"], "statements": ["The GC mRNA expression and clinical data were obtained from the TCGA data portal (https://portal.gdc.cancer.gov/). There were 407 patients with mRNA expression and clinical data. After excluding the normal tissues and patients with less than 1-month follow-up, 334-patient cohort from the TCGA dataset was used in this study."], "basis": "The paper names GSE84437, GSE54129 in Gene Expression Omnibus and the accession resolves in the repository. 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Immunochemistry (IHC) was used to examine the expression of CYP19", "ter and reliability predictive accuracy. The IHC data validate that high expression of CYP19A", "adjacent normal tissues among 24 patients by immunohistochemistry, scale bar=100 μm. (E) Different distributio", "gastric cancer. As shown in Figure 4D and E, IHC results indicated that the expression of CYP"], "order_basis": "paper_text_order:816", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["sm-Related Genes in GC Sample Gastric cancer RNA-seq expression data from 1025 samples were extra"], "order_basis": "paper_text_order:2567", "id": "assay:2"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["r stage (T,N) and gender (Table 2). 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