Multi-Omics Analysis Reveals the Role of Changes in Platelet Activation Pathways in the Survival Outcome of Patients with Esophageal Squamous Cell Carcinoma.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-10-01

Huiqing Wang, Zhenyan Li, Xiaodong Yao, Liang Cheng, Qingyuan Liu, Qiao Hu, Quanxi Zhou, Qingmei Yang, Haodong He, Shuyu Cai, Lu Fang, Ke Li, Zhaomeng Wang, Hongying Wen, Chunyang Zhou, Maoyong Fu, Chunmei Cao

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Abstract

Objective: The objective of this study was to integrate metabolomics and transcriptomics data to identify key diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC). Plasma samples were collected from 85 ESCC patients at different stages and 50 healthy volunteers for non-targeted metabolomic analysis.

Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for non-targeted metabolomic analysis. Subsequently, we integrated the metabolomic data with transcriptomic data from the Gene Expression Omnibus (GEO) and prognosis data from The Cancer Genome Atlas Program (TCGA) to perform pathway analysis. Our focus was on pathways that involve both metabolites and upstream genes, as they often exhibit higher accuracy.

Results: Through the integration of metabolomics and transcriptomics, we identified significant alterations in the platelet activation pathway in ESCC. This pathway involves the participation of both metabolites and genes, making it a more accurate reflection of pathological changes associated with the disease. Notably, metabolite arachidonic acid (AA) and chemokine receptor type 2(CXCR2) were significantly downregulated in ESCC, while genes collagen type I alpha 1(COL1A1), collagen type I alpha 2(COL1A2), collagen type III alpha 1(COL3A1), type 3 inositol 1,4,5-trisphosphate receptor (ITPR3), and insulin-like growth factor II mRNA binding protein 3(IGF2BP3) were significantly upregulated, indicating the presence of tumor-induced platelet activation in ESCC. Further analysis of prognosis data revealed that high expression of COL1A1, IGF2BP3, and ITPR3 was associated with a favorable prognosis for ESCC, while high CXCR2 expression was linked to an adverse prognosis. In addition, we combined COL1A1, ITPR3, IGF2BP3, CXCR2, and AA to form a diagnostic biomarker panel. The receiver operating characteristic curve (ROC) demonstrated excellent diagnostic capability (AUC=0.987).

Conclusion: Our study underscores the significant role of platelet activation pathways and related genes in the diagnosis and prognosis of ESCC patients. These findings offer promising insights for improving the clinical management of ESCC.

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多指标分析揭示血小板活化途径变化在食管鳞状细胞癌患者生存结果中的作用

研究目的本研究旨在整合代谢组学和转录组学数据，以确定食管鳞状细胞癌（ESCC）的关键诊断和预后标记物。研究收集了85名处于不同阶段的ESCC患者和50名健康志愿者的血浆样本，进行非靶向代谢组学分析：方法：采用液相色谱-串联质谱法（LC-MS/MS）进行非靶向代谢组学分析。随后，我们将代谢组数据与基因表达总库（Gene Expression Omnibus，GEO）的转录组数据和癌症基因组图谱计划（The Cancer Genome Atlas Program，TCGA）的预后数据整合在一起，进行通路分析。我们的重点是同时涉及代谢物和上游基因的通路，因为它们通常表现出更高的准确性：通过整合代谢组学和转录组学，我们发现了 ESCC 中血小板活化通路的显著变化。该通路涉及代谢物和基因的参与，因此能更准确地反映与疾病相关的病理变化。3型肌醇1,4,5-三磷酸受体（ITPR3）和胰岛素样生长因子II mRNA结合蛋白3（IGF2BP3）显著上调，表明ESCC中存在肿瘤诱导的血小板活化。对预后数据的进一步分析表明，COL1A1、IGF2BP3和ITPR3的高表达与ESCC的良好预后相关，而CXCR2的高表达与不良预后相关。此外，我们还将 COL1A1、ITPR3、IGF2BP3、CXCR2 和 AA 结合在一起，形成了一个诊断生物标记物面板。接受者操作特征曲线（ROC）显示了极佳的诊断能力（AUC=0.987）：我们的研究强调了血小板活化途径和相关基因在 ESCC 患者的诊断和预后中的重要作用。结论：我们的研究强调了血小板活化通路和相关基因在 ESCC 患者诊断和预后中的重要作用，这些发现为改善 ESCC 的临床治疗提供了很好的启示。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.