Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2018; 24(33): 3760-3769
Published online Sep 7, 2018. doi: 10.3748/wjg.v24.i33.3760
Metabolomic alterations and chromosomal instability status in gastric cancer
Cheng-Kun Tsai, Ta-Sen Yeh, Ren-Chin Wu, Ying-Chieh Lai, Meng-Han Chiang, Kuan-Ying Lu, Cheng-Yu Hung, Hung-Yao Ho, Mei-Ling Cheng, Gigin Lin
Cheng-Kun Tsai, Meng-Han Chiang, Hung-Yao Ho, Mei-Ling Cheng, Gigin Lin, Clinical Metabolomics Core Lab, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan 333, Taiwan
Cheng-Kun Tsai, Ying-Chieh Lai, Meng-Han Chiang, Kuan-Ying Lu, Cheng-Yu Hung, Gigin Lin, Department of Medical Imaging and Intervention, Imaging Core Lab, Institute for Radiological Research, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan 333, Taiwan
Ta-Sen Yeh, Department of Surgery, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan 333, Taiwan
Ren-Chin Wu, Department of Pathology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan 333, Taiwan
Hung-Yao Ho, Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
Mei-Ling Cheng, Department of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
Author contributions: Lin G conceived and designed the experiments; Yeh TS, Chiang MH, Lu KY and Hung CY performed the experiments; Tsai CK and Chiang MH analyzed the data; Wu RC, Lai YC, Ho HY and Cheng ML contributed reagents/materials/analysis tools; Tsai CK and Lin G wrote the paper.
Supported by the Ministry of Science and Technology Taiwan grant, No. MOST 106-2314-B-182A-019-MY3; the Chang Gung Foundation, No. CMRPG3E1321-2, No. IRB201601916B0, and No. IRB103-7448B.
Institutional review board statement: All procedures in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Gigin Lin, MD, PhD, Associate Professor, Department of Medical Imaging and Intervention, Imaging Core Lab, Institute for Radiological Research, Chang Gung Memorial Hospital at Linkou and Chang Gung University, No. 5, Fuxing St., Guishan Dist., Taoyuan 333, Taiwan. giginlin@cgmh.org.tw
Telephone: +886-3-3281200 Fax: +886-3-3971936
Received: May 22, 2018
Peer-review started: May 23, 2018
First decision: June 13, 2018
Revised: June 27, 2018
Accepted: July 16, 2018
Article in press: July 16, 2018
Published online: September 7, 2018
Abstract
AIM

To explore the correlation of metabolomics profiles of gastric cancer (GC) with its chromosomal instability (CIN) status.

METHODS

Nineteen GC patients were classified as CIN and non-CIN type by The Cancer Genome Atlas Research Group system, based on 409 oncogenes and tumor suppressor genes sequenced. The aqueous metabolites of the GC tumor and its surrounding adjacent healthy tissues were identified through liquid chromatography-mass spectrometry. Groups were compared by defining variable importance in projection score of > 1.2, a fold change value or its reciprocal of > 1.2, and a P value of < 0.05 as a significant difference.

RESULTS

In total, twelve men and seven women were enrolled, with a median age of 66 years (range, 47-87 years). The numbers of gene alterations in the CIN GC group were significantly higher than those in the non-CIN GC (32-218 vs 2-17; P < 0.0005). Compared with the adjacent healthy tissues, GC tumors demonstrated significantly higher aspartic acid, citicoline, glutamic acid, oxidized glutathione, succinyladenosine, and uridine diphosphate-N-acetylglucosamine levels, but significantly lower butyrylcarnitine, glutathione hydroxyhexanoycarnitine, inosinic acid, isovalerylcarnitine, and threonine levels (all P < 0.05). CIN tumors contained significantly higher phosphocholine and uridine 5’-monophosphate levels but significantly lower beta-citryl-L-glutamic acid levels than did non-CIN tumors (all P < 0.05). CIN GC tumors demonstrated additional altered pathways involving alanine, aspartate, and glutamate metabolism, glyoxylate and dicarboxylate metabolism, histidine metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis.

CONCLUSION

Metabolomic profiles of GC tumors and the adjacent healthy tissue are distinct, and the CIN status is associated with downstream metabolic alterations in GC.

Keywords: Gastric cancer, Metabolomics, Oncogene, Copy-number, Chromosomal instability, Liquid chromatography-mass spectrometry

Core tip: We studied the correlation of the comprehensive metabolomic profiles of gastric cancer with its chromosomal instability (CIN) status. In this disease landscape study with no pre-specified hypothesis, we combined a gene molecule classification method with a metabolomics method to discover metabolic information for accurate tumor classification. CIN status-based metabolomic profiling has demonstrated translational potential in biomarker discovery and novel therapeutics development.