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基于液相色谱-质谱联用的血清代谢组学分析用于结直肠癌的筛查与监测

LC-MS-based serum metabolomics analysis for the screening and monitoring of colorectal cancer.

作者信息

Yi Yanan, Wang Jianjian, Liang Chengtong, Ren Chuanli, Lian Xu, Han Chongxu, Sun Wei

机构信息

Department of Laboratory Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, China.

Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.

出版信息

Front Oncol. 2023 Jun 28;13:1173424. doi: 10.3389/fonc.2023.1173424. eCollection 2023.

DOI:10.3389/fonc.2023.1173424
PMID:37448516
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10338013/
Abstract

BACKGROUND

Colorectal Cancer (CRC) is a prevalent digestive system tumour with significant mortality and recurrence rates. Serum metabolomics, with its high sensitivity and high throughput, has shown potential as a tool to discover biomarkers for clinical screening and monitoring of the CRC patients.

METHODS

Serum metabolites of 61 sex and age-matched healthy controls and 62 CRC patients (before and after surgical intervention) were analyzed using a ultra-performance liquid chromatography-high resolution mass spectrometer (UPLC-MS). Statistical methods and pathway enrichment analysis were used to identify potential biomarkers and altered metabolic pathways.

RESULTS

Our analysis revealed a clear distinction in the serum metabolic profile between CRC patients and healthy controls (HCs). Pathway analysis indicated a significant association with arginine biosynthesis, pyrimidine metabolism, pantothenate, and CoA biosynthesis. Univariate and multivariate statistical analysis showed that 9 metabolites had significant diagnostic value for CRC, among them, Guanosine with Area Under the Curve (AUC) values of 0.951 for the training group and0.998 for the validation group. Furthermore, analysis of four specific metabolites (N-Phenylacetylasparticacid, Tyrosyl-Gamma-glutamate, Tyr-Ser and Sphingosine) in serum samples of CRC patients before and after surgery indicated a return to healthy levels after an intervention.

CONCLUSION

Our results suggest that serum metabolomics may be a valuable tool for the screening and monitoring of CRC patients.

摘要

背景

结直肠癌(CRC)是一种常见的消化系统肿瘤,死亡率和复发率都很高。血清代谢组学具有高灵敏度和高通量的特点,已显示出作为发现生物标志物以用于CRC患者临床筛查和监测工具的潜力。

方法

使用超高效液相色谱-高分辨率质谱仪(UPLC-MS)分析了61名年龄和性别匹配的健康对照者以及62名CRC患者(手术干预前后)的血清代谢物。采用统计方法和通路富集分析来识别潜在的生物标志物和改变的代谢通路。

结果

我们的分析揭示了CRC患者和健康对照者(HCs)血清代谢谱存在明显差异。通路分析表明与精氨酸生物合成、嘧啶代谢、泛酸和辅酶A生物合成有显著关联。单变量和多变量统计分析表明,9种代谢物对CRC具有显著的诊断价值,其中鸟苷在训练组的曲线下面积(AUC)值为0.951,在验证组为0.998。此外,对CRC患者手术前后血清样本中四种特定代谢物(N-苯基乙酰天冬氨酸、酪氨酰-γ-谷氨酸、酪氨酰-丝氨酸和鞘氨醇)的分析表明,干预后这些代谢物水平恢复到健康水平。

结论

我们的结果表明,血清代谢组学可能是CRC患者筛查和监测的有价值工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b89/10338013/1742b402f496/fonc-13-1173424-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b89/10338013/f93b52f3be15/fonc-13-1173424-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b89/10338013/84696ba97759/fonc-13-1173424-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b89/10338013/1742b402f496/fonc-13-1173424-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b89/10338013/f93b52f3be15/fonc-13-1173424-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b89/10338013/84696ba97759/fonc-13-1173424-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b89/10338013/1742b402f496/fonc-13-1173424-g003.jpg

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