扶正抗癌方治疗肝癌肝郁脾虚瘀毒证的血清代谢组学研究

Serum metabolomics study on the effect of Fuzheng Kangai Formula on liver cancer with liver stagnation,spleen deficiency,stasis and toxin syndrome

目的:探讨扶正抗癌方治疗肝癌肝郁脾虚瘀毒证患者的血清代谢差异物、潜在生物标志物及代谢通路。方法:选择2021年05月至2022年07月于某院就诊的12例原发性肝癌患者和12例健康受试者为研究对象,收集健康受试者及扶正抗癌方治疗前后肝癌患者血清标本,以超高效液相色谱串联质谱为检测手段进行全谱代谢组学分析,应用主成分分析、最小二乘判别分析及单变量统计分析方法分析健康组、治疗前组及治疗后组血清代谢物的变化,筛选差异代谢物及重要代谢通路。结果:研究共纳入36例血清标本,其中健康对照组12例,扶正抗癌方干预前、后各12例。代谢组学结果提示:筛选出健康对照组和扶正抗癌方治疗前组差异代谢物共570个;健康对照组和扶正抗癌方治疗后组差异代谢物共571个;扶正抗癌方干预前后差异代谢物共74个,其中上调37个,下调37个,显著差异代谢产物14个,主要富集在抗坏血酸和醛酸代谢、苯丙氨酸代谢、辅因子生物合成、肌醇磷酸代谢、缬氨酸、亮氨酸和异亮氨酸生物合成通路。结论:本研究筛选出扶正抗癌方治疗前、后显著改变的14种差异代谢物,并对这些代谢物进行了主要的富集通路、调控网络和作用机制分析,从中西医结合的角度为扶正抗癌方对晚期肝郁脾虚瘀毒证肝癌患者的作用机制提供了新的见解。

Objective:To explore the effects of Fuzheng Kangai Formula on serum metabolic abnormalities,potential biomarkers,and metabolic pathways in patients with liver cancer with liver stagnation,spleen deficiency,and stasis toxin syndrome.Methods:Twelve healthy subjects and primary liver cancer patients who came to a hospital from May 2021 to July 2022 were selected as the research subjects.Serum samples of healthy individuals and liver cancer patients before and after treatment with Fuzheng Kangai Formula were collected,and full spectrum metabolomics analysis was performed using ultra-high performance liquid chromatography and tandem mass spectrometry.Principal component analysis,least squares discriminant analysis,and univariate statistical analysis were used to determine the content of relevant metabolic markers.Results:The study included serum samples from 36 patients,including 12 healthy control group and 12 cases before and after the intervention of Fuzheng Kangai Formula.The metabolomics results suggest that a total of 570 differential metabolites were screened from the healthy control group and the pre-treatment group with Fuzheng Kangai Formula.There are a total of 571 differential metabolites between the healthy control group and the post-treatment group with Fuzheng Kangai Formula.There are a total of 74 differential metabolites before and after the intervention of Fuzheng Kangai Formula,of which 37 are upregulated,37 are downregulated,and 14 are significantly different metabolites,mainly enriched in the metabolism of ascorbic acid and arabinose,phenylalanine metabolism,cofactor biosynthesis,inositol phosphate metabolism,and the biosynthesis pathways of valine leucine and isoleucine.Conclusion:This study screened 14 differential metabolites that showed significant changes before and after treatment,and analyzed the main enrichment pathways,regulatory networks,and mechanisms of action of these metabolites.From the perspective of integrated traditional Chinese and Western medicine,new insights were provided for the mechanism of action of Fuzheng Kangai Formula in treating liver cancer patients with advanced liver stagnation,spleen deficiency,and stasis toxin syndrome.