脂肪酸合成代谢通路差异性代谢标志物与鼻咽癌发病相关性研究  

Study of the differential metabolites in the fatty acid synthesis pathway related to nasopharyngeal carcinoma pathogenesis

作　　者：韩艳艳 周珺珺 周中铭 陈珏[1] 黄水仙 HANYanyan;ZHOU Junjun;ZHOU Zhongming;CHEN Jue;HUANG Shuixian(Department of Otolaryngology,Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200125,China)

机构地区：[1]上海交通大学医学院附属仁济医院浦南分院耳鼻咽喉科,200125 [2]上海交通大学医学院附属仁济医院放疗科,200125 [3]上海市浦东新区公利医院耳鼻咽喉科

出　　处：《中国中西医结合耳鼻咽喉科杂志》2025年第2期81-88,共8页Chinese Journal of Otorhinolaryngology in Integrative Medicine

基　　金：上海市浦东新区科技发展基金事业单位民生科研专项(医疗卫生)项目(PKJ2022-Y83);上海市浦东新区卫生系统学科建设项目:周围性眩晕特色专病项目(PWZzb2022-27);上海市浦东新区卫生健康委员会领先人才项目(PWRl2021-07);上海市浦东新区“国家中医药发展综合改革试验区”中西医结合高级人才培养项目(PDZY-2024-0713)。

摘　　要：目的使用HILIC UHPLC-Q-EXACTIVE MS代谢组学方法及差异性代谢标志物生物信息学和代谢网络分析,探索鼻咽癌发病相关血清脂肪酸合成通路代谢标志物变化。方法选取2020年10月~2023年11月在上海交通大学医学院附属仁济医院浦南分院和上海交通大学医学院附属仁济医院放疗科经鼻内镜病理活检确诊的30例NPC患者为病例组,同时收集30例正常鼻咽黏膜组作为对照组。研究对象外周血经UHPLC预处理分离后用Q-EXACTIVE MS质谱检测,通过PCA分析、PLS-DA及OPLS-DA建模分析差异性代谢标志物,并经聚类分析和KEGG代谢通路分析探讨鼻咽癌患者脂肪酸合成代谢通路差异表达代谢物变化。结果PCA分析结果表明,鼻咽癌组代谢谱相对于对照组发生了变化,P<0.05。正、负离子模式数据建立的PLS-DA、OPLS-DA模型,R2、Q2≥0.5,模型稳定可靠。以OPLS-DA模型VIP>1且P值<0.05为筛选标准,筛选鼻咽癌发病相关显著性差异代谢物。随后经聚类分析结果提示两组存在显著差异的代谢标志物有脂肪酸合成代谢通路差异表达代谢物、中心碳代谢相关代谢物、咖啡因代谢相关标志物;对脂肪酸差异性代谢标志物分析,肉豆蔻酸、棕榈酸在阴离子和阳离子模式下两组差异均有统计学意义(P<0.05),KEGG代谢通路分析提示脂肪酸代谢通路中肿瘤发病相关AMPK通路下游调节因子乙酰辅酶ACC磷酸化及FASN参与肉豆蔻酸、棕榈酸等脂肪酸合成。结论鼻咽癌中脂肪酸合成代谢通路相关代谢物存在明显的差异表达,这些差异表达的代谢物可能通过调控肿瘤发病相关代谢网络参与鼻咽癌的发生、发展,为鼻咽癌早期诊断标志物探索及发病机制研究提供了新的方向。Objective To explore the changes in metabolic markers related to serum fatty acid synthesis pathway in nasopharyngeal carcinoma using HILIC UHPLC-Q-EXACTIVE MS metabolomics method and differential metabolic biomarker bioinformatics and metabolic network analysis.Method Patients who underwent surgery or were diagnosed with nasopharyngeal carcinoma through nasal endoscopy in the department of Otolaryngology of Punan Branch of Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the Radiotherapy department of Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from October 2020 to November 2023 were selected as the case group,meanwhile,patients diagnosed with normal nasopharyngeal mucosal through endoscopy were selected as the control group.The peripheral blood samples were preprocessed and separated by UHPLC and detected by Q-EXACTIVE MS mass spectrometry.Differential metabolic markers were analyzed through PCA analysis,PLS-DA,and OPLS-DA modeling.Cluster analysis and KEGG metabolic pathway analysis were used to explore the differential metabolites in the fatty acid synthesis metabolic pathway in nasopharyngeal carcinoma patients.Result The PCA analysis results demonstrated that the metabolic profile of the nasopharyngeal carcinoma group changed statistically significant than the control group,P<0.05.The PLS-DA and OPLS-DA models established based on positive and negative ion mode data had R2 and Q2≥0.5,indicating stable and reliable models.Using the OPLS-DA model with VIP>1 and P value<0.05 as the screening criteria,significant differential metabolites related to the incidence of nasopharyngeal carcinoma were screened.Subsequently,cluster analysis revealed significant differences in metabolic markers between the two groups,including differentially expressed metabolites in fatty acid synthesis pathways,central carbon metabolism related metabolites,and caffeine metabolism related markers.Analysis of differential metabolic markers of fatty acids showed that the

关 键 词：鼻咽癌 代谢标志物 脂肪酸 代谢通路 

分 类 号：R739.63[医药卫生—肿瘤]