关键词: Cell proliferation and invasion Gastric cancer Gene Ontology MTTP Triphenyl phosphate

来  源:   DOI:10.1016/j.ecoenv.2024.116618

Abstract:
BACKGROUND: Gastric cancer is a leading cause of cancer-related deaths influenced by both genetic and environmental factors. Triphenyl phosphate (TPP) is a prevalent flame retardant, but its health implications remain to be thoroughly understood.
OBJECTIVE: To explore the link between TPP exposure and gastric cancer by examining gene expression patterns and developing a predictive model.
METHODS: Gene expression data were sourced from The Cancer Genome Atlas (TCGA) and the Comparative Toxicogenomics Database (CTD). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were employed for analysis. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to obtain phosphate flame retardant-related scores. A predictive model was constructed through differential analysis, univariate COX regression, and LASSO regression. Molecular docking was performed to assess protein interactions with TPP.
RESULTS: ssGSEA identified scores related to phosphate flame retardants in gastric cancer, which had a strong association with immune-related traits. Several genes associated with TPP were identified and used to develop a prognostic model that has clinical significance. Molecular docking showed a high binding affinity of TPP with MTTP, a gene related to lipid metabolism. Pathway analysis indicated that TPP exposure contributes to gastric cancer through lipid metabolic processes.
CONCLUSIONS: The study establishes a potential correlation between TPP exposure and gastric cancer onset, pinpointing key genes and pathways involved. This underscores the significance of environmental factors in gastric cancer research and presents a potential diagnostic tool for clinical application.
摘要:
背景:胃癌是受遗传和环境因素影响的癌症相关死亡的主要原因。磷酸三苯酯(TPP)是一种普遍使用的阻燃剂,但其对健康的影响仍有待彻底理解。
目的:通过检测基因表达模式和建立预测模型,探索TPP暴露与胃癌之间的联系。
方法:基因表达数据来源于癌症基因组图谱(TCGA)和比较毒性基因组学数据库(CTD)。采用基因本体论(GO)和京都基因和基因组百科全书(KEGG)途径进行分析。单样品基因组富集分析(ssGSEA)用于获得磷酸酯阻燃剂相关评分。通过差异分析构建了预测模型,单变量COX回归,和LASSO回归。进行分子对接以评估蛋白质与TPP的相互作用。
结果:ssGSEA确定了与胃癌中磷酸盐阻燃剂相关的分数,与免疫相关的性状有很强的相关性。鉴定了几种与TPP相关的基因,并将其用于开发具有临床意义的预后模型。分子对接显示了TPP与MTTP的高结合亲和力,与脂质代谢有关的基因。通路分析表明,TPP暴露通过脂质代谢过程促进胃癌的发生。
结论:该研究建立了TPP暴露与胃癌发病之间的潜在相关性,精确定位涉及的关键基因和途径。这强调了环境因素在胃癌研究中的重要性,并为临床应用提供了潜在的诊断工具。
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