结直肠癌患者尿液中20种氨基酸靶向代谢组特征研究
Targeted metabolomic characteristics of 20 amino acids in urine of colorectal cancer
祁峰 1孙玉琳 2刘佳琦 3郭正光 1刘晓燕 1孙海丹 1何成彦 3赵晓航 2孙伟1
作者信息
- 1. 中国医学科学院基础医学研究所·北京协和医学院基础学院药理系,北京 100005
- 2. 国家癌症中心·国家癌症临床研究中心·中国医学科学院癌症医院分子肿瘤国家重点实验室,北京 100021
- 3. 吉林大学中日联谊医院检验科,吉林 长春 130033
- 折叠
摘要
目的 探究20种常见氨基酸在结直肠癌(CRC)患者的尿液特征;寻找CRC诊断的生物学标志物.方法 纳入100名健康对照者和113名CRC患者(Ⅰ期27例,Ⅱ期28例,Ⅲ期34例,Ⅳ期24例),基于超高效液相色谱串联质谱法对尿液中的20种常见氨基酸应用多反应监测技术进行靶向定量分析,应用统计学方法分析CRC患者与健康对照氨基酸含量差异,并构建CRC诊断模型.结果 CRC患者尿液中 16种氨基酸含量与健康对照差异有统计学意义,Ⅰ,Ⅱ,Ⅲ和Ⅳ期各自有9种,15种,14种,17种氨基酸含量与健康对照差异有统计学意义.由异亮氨酸,天冬酰胺,脯氨酸,组氨酸,酪氨酸,苯丙氨酸6种氨基酸构建的生物标志物组合用于CRC诊断的AUC值在发现组/验证组分别为0.857/0.851,在Ⅰ,Ⅱ,Ⅲ和Ⅳ期CRC的AUC值分别为0.847,0.843,0.897,0.896.结论 尿液中20种氨基酸含量变化可以用于CRC诊断,为CRC的早期诊断提供了新的研究思路.
Abstract
Objective To investigate the urinary characteristics of 20 amino acids in patients with colorectal cancer(CRC);Constructing a biomarker panel for CRC diagnosis.Methods 100 healthy controls and 113 CRC patients were enrolled(27 in stage Ⅰ,28 in stage Ⅱ,34 in stage Ⅲ and 24 in stage Ⅳ).Targeted quantitative analysis of 20 common amino acids in urine was performed using multiple reaction monitoring technology based on ultra-high performance liq-uid chromatography tandem mass spectrometry(UPLC-MS/MS).Statistical methods were used to analyze the differ-ences in amino acids content between CRC patients and healthy controls,and a CRC diagnostic model was constructed.Results There was a statistical significance in the content of 16 amino acids in CRC urine compared to healthy con-trols,and 9,15,14,and 17 amino acids in Stage Ⅰ,Ⅱ,Ⅲ and Ⅳ showed a statistical difference.A biomarker panel composed of six amino acids,isoleucine,asparagine,proline,histidine,tyrosine,and phenylalanine was constructed for CRC diagnosis.The AUC in the discovery/validation group were 0.857/0.851,and in the Stage Ⅰ/Ⅱ/Ⅲ/Ⅳ of CRC,the AUC value was 0.847/0.843/0.897/0.896,respectively.Conclusion Changes in the content of 20 amino acids in urine can be used for the diagnosis of CRC,and this study provides new research ideas for the diagnosis of CRC.
关键词
氨基酸/尿液/靶向分析/结直肠癌Key words
amino acids/urine/targeted analysis/colorectal cancer引用本文复制引用
基金项目
中国医科院医学科学创新基金(2021-I2M-1-016)
中国医科院医学科学创新基金(2021-I2M-1-066)
中国医科院医学科学创新基金(2022-I2M-1-020)
出版年
2024