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用于人类结直肠癌诊断和预后的组织代谢组学表型分析

Tissue Metabonomic Phenotyping for Diagnosis and Prognosis of Human Colorectal Cancer.

作者信息

Tian Yuan, Xu Tangpeng, Huang Jia, Zhang Limin, Xu Shan, Xiong Bin, Wang Yulan, Tang Huiru

机构信息

CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, China.

Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

出版信息

Sci Rep. 2016 Feb 15;6:20790. doi: 10.1038/srep20790.

DOI:10.1038/srep20790
PMID:26876567
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4753490/
Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide and prognosis based on the conventional histological grading method for CRC remains poor. To better the situation, we analyzed the metabonomic signatures of 50 human CRC tissues and their adjacent non-involved tissues (ANIT) using high-resolution magic-angle spinning (HRMAS) (1)H NMR spectroscopy together with the fatty acid compositions of these tissues using GC-FID/MS. We showed that tissue metabolic phenotypes not only discriminated CRC tissues from ANIT, but also distinguished low-grade tumor tissues (stages I-II) from the high-grade ones (stages III-IV) with high sensitivity and specificity in both cases. Metabonomic phenotypes of CRC tissues differed significantly from that of ANIT in energy metabolism, membrane biosynthesis and degradations, osmotic regulations together with the metabolism of proteins and nucleotides. Amongst all CRC tissues, the stage I tumors exhibited largest differentiations from ANIT. The combination of the differentiating metabolites showed outstanding collective power for differentiating cancer from ANIT and for distinguishing CRC tissues at different stages. These findings revealed details in the typical metabonomic phenotypes associated with CRC tissues nondestructively and demonstrated tissue metabonomic phenotyping as an important molecular pathology tool for diagnosis and prognosis of cancerous solid tumors.

摘要

结直肠癌（CRC）是全球癌症相关死亡的主要原因之一，基于传统组织学分级方法的CRC预后仍然较差。为改善这种情况，我们使用高分辨率魔角旋转（HRMAS）氢核磁共振波谱分析了50个人类CRC组织及其相邻未受累组织（ANIT）的代谢组学特征，并使用气相色谱 - 火焰离子化检测器/质谱联用仪分析了这些组织的脂肪酸组成。我们发现，组织代谢表型不仅能将CRC组织与ANIT区分开来，而且在两种情况下都能以高灵敏度和特异性将低级别肿瘤组织（I-II期）与高级别肿瘤组织（III-IV期）区分开来。CRC组织的代谢组学表型在能量代谢、膜生物合成与降解、渗透调节以及蛋白质和核苷酸代谢方面与ANIT有显著差异。在所有CRC组织中，I期肿瘤与ANIT的差异最大。这些具有区分作用的代谢物组合在区分癌症与ANIT以及区分不同阶段的CRC组织方面显示出强大的集体能力。这些发现无损地揭示了与CRC组织相关的典型代谢组学表型的细节，并证明组织代谢组学表型分析是一种用于诊断和预测实体癌的重要分子病理学工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4273/4753490/19fa66ebccfd/srep20790-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4273/4753490/6438acc6f215/srep20790-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4273/4753490/d40814eafe74/srep20790-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4273/4753490/2bf985e5c1f5/srep20790-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4273/4753490/5a1fa0948117/srep20790-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4273/4753490/612246d1a6d4/srep20790-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4273/4753490/19fa66ebccfd/srep20790-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4273/4753490/6438acc6f215/srep20790-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4273/4753490/d40814eafe74/srep20790-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4273/4753490/2bf985e5c1f5/srep20790-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4273/4753490/5a1fa0948117/srep20790-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4273/4753490/612246d1a6d4/srep20790-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4273/4753490/19fa66ebccfd/srep20790-f6.jpg

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