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通过1H NMR评估的结直肠癌淋巴结转移的组织代谢谱分析

Tissue metabolic profiling of lymph node metastasis of colorectal cancer assessed by 1H NMR.

作者信息

Zhang Hailong, Qiao Liang, Li Xiaopeng, Wan Yang, Yang Li, Wang Huijuan

机构信息

Henan Engineering Laboratory of Antibody Medicine, Henan International United Laboratory of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Medical College, Henan University, Kaifeng, Henan 475004, P.R. China.

College of Life Science and Technology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.

出版信息

Oncol Rep. 2016 Dec;36(6):3436-3448. doi: 10.3892/or.2016.5175. Epub 2016 Oct 14.

DOI:10.3892/or.2016.5175
PMID:27748865
Abstract

Lymph node metastasis is a decisive prognostic and therapeutic staging factor for colorectal cancer (CRC), which is one of the most prevalent types of cancer and a malignant tumor. The metabolic profiling of tissue samples from a large cohort of lymph node non‑metastatic CRC patients (n=73), lymph node metastatic CRC patients (n=52) and normal controls (n=41) was performed using 1H nuclear magnetic resonance (NMR) together with multivariate statistical analyses. Excellent separation was obtained between CRC patients and normal controls, and CRC patients were also perfectly classified according to lymph node metastasis. Forty‑two distinguishing metabolites were identified, which revealed disturbance of glycolysis, glutaminolysis, fatty acid metabolism, choline metabolism and amino acids, suggesting that cellular functions in energy production, macromolecular synthesis, oxidative stress and immune escape of cancer cells are affected in CRC. In total, 10 tissue metabolites were significantly disturbed between non‑metastatic and metastatic CRC patients. The present study firstly staged CRC patients by lymph node metastasis by metabolomic approach. The identified metabolites may be associated with the neoplasia, invasion and metastasis of the tumor. The results suggest the promising application of these metabolites in clinical therapy, and further understanding of the related mechanism warrants further investigation.

摘要

淋巴结转移是结直肠癌(CRC)预后和治疗分期的决定性因素,结直肠癌是最常见的癌症类型之一,是一种恶性肿瘤。使用1H核磁共振(NMR)结合多变量统计分析,对大量淋巴结无转移的CRC患者(n = 73)、淋巴结转移的CRC患者(n = 52)和正常对照(n = 41)的组织样本进行代谢谱分析。CRC患者与正常对照之间实现了良好的区分,CRC患者也根据淋巴结转移情况得到了完美分类。鉴定出42种有区别的代谢物,揭示了糖酵解、谷氨酰胺分解、脂肪酸代谢、胆碱代谢和氨基酸的紊乱,表明CRC中癌细胞的能量产生、大分子合成、氧化应激和免疫逃逸中的细胞功能受到影响。总体而言,非转移性和转移性CRC患者之间有10种组织代谢物受到显著干扰。本研究首次通过代谢组学方法根据淋巴结转移对CRC患者进行分期。鉴定出的代谢物可能与肿瘤的发生、侵袭和转移有关。结果表明这些代谢物在临床治疗中有广阔的应用前景,对相关机制的进一步了解值得进一步研究。

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