文章摘要
Ⅲ、Ⅳ期胃癌脾胃气虚证与非脾胃气虚证患者血清物质差异的多组学研究
Multi-omics Study on Serum Substance Differences Between Patients with Spleen-Stomach Qi Deficiency Syndrome and Non-Spleen-Stomach Qi Deficiency Syndrome in Stage Ⅲ and Ⅳ Gastric Cancer
DOI:
中文关键词: 胃癌  代谢组学  蛋白组学  中医证型  脾胃气虚证  
英文关键词: Gastric cancer  Metabolomics  Proteomics  Traditional Chinese Medicine syndrome types  Spleen-stomach qi deficiency syndrome  
基金项目:扬州市科技计划项目(批准号YZ2023064);江苏省中医药科技发展计划项目(批准号ZD202013);第四批江苏省名老中医专家张晓春学术传承工作室建设项目(批准号GZS20220628001);国家中医优势专科建设单位(批准号GJZYYSZKJS-ZLK)
作者单位邮编
刘真理 南京中医药大学扬州附属医院 225100
周雲霞 南京中医药大学扬州附属医院 
何莉 南京中医药大学扬州附属医院 
葛志颖 南京中医药大学扬州附属医院 
李念 扬州大学医学院 
张晓春* 扬州市中医院 
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中文摘要:
      摘要 目的 基于非靶代谢组学、定量蛋白组学探究Ⅲ、Ⅳ期胃癌脾胃气虚证和非脾胃气虚证之间的标志性血清代谢物与显著差异蛋白。 方法 本研究共收集16例Ⅲ、Ⅳ期胃癌患者的血浆样本,其中脾胃气虚证8例、非脾胃气虚证8例。应用样本的代谢物提取、LC-MS检测、数据分析、谱图处理及数据库搜库、多元统计等技术进行非靶代谢组学分析;应用蛋白质提取、肽段酶解、质谱检测、数据检索及蛋白质定量分析等技术进行蛋白组学的研究。最终确定Ⅲ、Ⅳ期胃癌脾胃气虚证与非脾胃气虚证之间的标志性血清代谢物和显著差异蛋白。 结果 代谢组学研究中,胃癌脾胃气虚证组和非脾胃气虚证组患者间共有61个代谢物差异显著,其中17个代谢物上调,44个代谢物下调;正离子富集到谷胱甘肽代谢、ABC转运蛋白、精氨酸和脯氨酸代谢等13条代谢通路,负离子富集到甘油脂类代谢、磷脂酶D信号通路、脂肪的消化和吸收等20条代谢通路。 蛋白组学研究中,脾胃气虚证组和非脾胃气虚证组胃癌患者间共有84个蛋白质的表达水平发生显著性变化,其中血清白蛋白、补体6、血清纤维胶凝蛋白3等27个蛋白质的表达显著性升高,免疫球蛋白、前组织蛋白酶H、Ig重链可变区(片段)等57个蛋白质的表达明显降低。 结论 Ⅲ、Ⅳ期胃癌脾胃气虚证与非脾胃气虚证之间会出现血清代谢物质差异与蛋白差异,这可能与不同证型胃癌的物质基础和胃癌的发病机制有关,多组学技术相结合,用现代科学技术为中医学“辨证论治”的理念提供了科学的可视化途径,对推动祖国医学的进一步发展有着重要意义。
英文摘要:
      Abstract Objective Investigating signature serum metabolites and significantly differential proteins between spleen-stomach qi deficiency syndrome and non-spleen-stomach qi deficiency syndrome in stage III and IV gastric cancer based on untargeted metabolomics and quantitative proteomics. Methods This study collected plasma samples from a total of 16 patients with stage III and IV gastric cancer, including 8 cases with spleen-stomach qi deficiency syndrome and 8 cases without spleen-stomach qi deficiency syndrome. Non-targeted metabolomics analysis was performed using techniques such as metabolite extraction from samples, LC-MS detection, data analysis, spectral processing, database searching, and multivariate statistics. Proteomics research was conducted using techniques such as protein extraction, peptide digestion, mass spectrometry detection, data retrieval, and protein quantitative analysis. Ultimately, the study identified signature serum metabolites and significantly differential proteins between stage III and IV gastric cancer patients with and without spleen-stomach qi deficiency syndrome. Results In the metabolomics study, there were 61 significantly differential metabolites between the gastric cancer patients with spleen-stomach qi deficiency syndrome and those without, among which 17 metabolites were upregulated and 44 were downregulated. Positive ion enrichment analysis identified 13 metabolic pathways, including glutathione metabolism, ABC transporters, and arginine and proline metabolism. Negative ion enrichment analysis revealed 20 metabolic pathways, such as glycerolipid metabolism, phospholipase D signaling pathway, and fat digestion and absorption. In the proteomics study, 84 proteins showed significant expression differences between the gastric cancer patients with spleen-stomach qi deficiency syndrome and those without. Among them, the expression levels of 27 proteins, including serum albumin, complement C6, and ficolin-3, were significantly increased, while the expression levels of 57 proteins, such as immunoglobulins, pro-cathepsin H, and Ig heavy chain variable region (fragment), were significantly decreased. Conclusions There are differences in serum metabolites and proteins between patients with stage Ⅲ and Ⅳ gastric cancer presenting with spleen-stomach qi deficiency syndrome and those without, which may be related to the material basis of different syndrome types and the pathogenesis of gastric cancer. The integration of multi-omics technologies provides a scientific and visual approach to the concept of "syndrome differentiation and treatment" in traditional Chinese medicine (TCM) using modern scientific techniques. This holds significant importance for advancing the further development of traditional Chinese medicine.
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