TGFBR2 as a prognostic marker and therapeutic target in benzo(a)pyrene-associated esophageal cancer: insights from multi-omics analysis.

IF 3.2 4区医学 Q1 Pharmacology, Toxicology and Pharmaceutics

Toxicology Mechanisms and Methods Pub Date : 2025-04-28 DOI:10.1080/15376516.2025.2495930

Hongying Zhou, Xiaochun Lv, Yun Chen, Zhiquan Qin

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引用次数: 0

Abstract

Background: Benzo(a)pyrene (BaP) is an environmental pollutant linked to several cancers, including esophageal cancer (ESCA). Understanding its impact on gene expression and associated molecular pathways in ESCA is crucial for developing targeted therapies.

Methods: Using the TCGA-ESCA dataset, we identified differentially expressed genes (DEGs) related to BaP exposure. Enrichment analyses and protein-protein interaction (PPI) network construction were performed to explore the biological significance of these DEGs. Molecular docking studies assessed the interactions between BaP and core subnetwork genes. Survival analysis and immune cell infiltration analysis were conducted to evaluate the prognostic value of TGFBR2. Chemotherapy drug sensitivity was analyzed based on TGFBR2 expression levels.

Results: We identified 5757 DEGs in ESCA, with 33 genes linked to both BaP exposure and ESCA. Enrichment analyses revealed significant pathways, including p53 signaling and apoptosis. Key genes (ACTB, CDKN2A, TGFBR2) were verified for their differential expression. Molecular docking demonstrated strong BaP binding to several core proteins. High TGFBR2 expression correlated with better survival, enhanced immune infiltration, and altered sensitivity to chemotherapeutic agents.

Conclusion: Our study highlights the molecular mechanisms by which BaP influences ESCA, with TGFBR2 emerging as a potential prognostic marker and therapeutic target. These insights pave the way for personalized treatments in BaP-induced esophageal carcinogenesis.

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TGFBR2作为苯并芘相关食管癌的预后标志物和治疗靶点：来自多组学分析的见解

背景：苯并(a)芘（BaP）是一种与多种癌症有关的环境污染物，包括食道癌（ESCA）。了解其对ESCA基因表达和相关分子途径的影响对于开发靶向治疗至关重要。方法：利用TCGA-ESCA数据集，我们鉴定了与BaP暴露相关的差异表达基因（DEGs）。通过富集分析和蛋白-蛋白相互作用（PPI）网络构建来探索这些deg的生物学意义。分子对接研究评估了BaP与核心子网络基因之间的相互作用。通过生存分析和免疫细胞浸润分析来评价TGFBR2的预后价值。根据TGFBR2表达水平分析化疗药物敏感性。结果：我们在ESCA中鉴定出5757个deg，其中33个基因与BaP暴露和ESCA相关。富集分析揭示了包括p53信号和细胞凋亡在内的重要途径。验证了关键基因ACTB、CDKN2A、TGFBR2的差异表达。分子对接表明，BaP与几个核心蛋白有很强的结合。高TGFBR2表达与更好的生存、增强的免疫浸润和对化疗药物的敏感性改变相关。结论：我们的研究强调了BaP影响ESCA的分子机制，TGFBR2成为潜在的预后标记物和治疗靶点。这些发现为bap诱导的食管癌的个性化治疗铺平了道路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology Mechanisms and Methods 医学-毒理学

CiteScore

6.60

自引率

3.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment.