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©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2019; 11(3): 181-194
Published online Mar 15, 2019. doi: 10.4251/wjgo.v11.i3.181
Glycerophospholipids pathways and chromosomal instability in gastric cancer: Global lipidomics analysis
Cheng-Yu Hung, Ta-Sen Yeh, Cheng-Kun Tsai, Ren-Chin Wu, Ying-Chieh Lai, Meng-Han Chiang, Kuan-Ying Lu, Chia-Ni Lin, Mei-Ling Cheng, Gigin Lin
Cheng-Yu Hung, Molecular Medicine Research Center, Chang Gung University, Taoyuan 333, Taiwan
Cheng-Yu Hung, Cheng-Kun Tsai, Ying-Chieh Lai, Meng-Han Chiang, Kuan-Ying Lu, Mei-Ling Cheng, Gigin Lin, Clinical Metabolomics Core Lab, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan 333, Taiwan
Cheng-Yu Hung, Cheng-Kun Tsai, Ying-Chieh Lai, Meng-Han Chiang, Kuan-Ying Lu, 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
Chia-Ni Lin, Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou and 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; Hung CY and Chiang MH analyzed the data; Wu RC, Lai YC, Lin CN and Cheng ML contributed reagents, materials, and analysis tools; Hung CY and Lin G wrote the paper.
Supported by the funding from the Ministry of Science and Technology Taiwan grant, No. MOST 106-2314-B-182A-019-MY3; and the Chang Gung Foundation, No. CMRPG3E1321-2.
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 declare that they have no conflict of interest.
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/
Corresponding author: Gigin Lin, MD, PhD, Director, Department of Medical Imaging and Intervention, Imaging Core Lab, Institute for Radiological Research, Metabolomics Core Lab, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Fuhsing 5, Taoyuan 333, Taiwan. giginlin@cgmh.org.tw
Telephone: +886-3-3281200-2575 Fax: +886-3-3971936
Received: November 15, 2018
Peer-review started: November 15, 2018
First decision: December 7, 2018
Revised: December 17, 2018
Accepted: December 23, 2018
Article in press: December 24, 2018
Published online: March 15, 2019
BACKGROUND
Based on the breakthrough of genomics analysis, The Cancer Genome Atlas Research Group recently proposed an integrative genomic analysis, dividing gastric cancer (GC) into four subtypes, characterized by the chromosomal instability (CIN) status. However, the CIN status of GC is still vaguely characterized and lacking the valuable easy-to-use CIN markers to diagnosis in molecular and histological detection.
AIM
To explore the associations of CIN with downstream lipidomics profiles.
METHODS
We collected cancerous and noncancerous tissue samples from 18 patients with GC; the samples were divided into CIN and non-CIN types based on the system of The Cancer Genome Atlas Research Group and 409 sequenced oncogenes and tumor suppressor genes. We identified the lipidomics profiles of the GC samples and samples of their adjacent noncancerous tissues by using liquid chromatography–mass spectrometry. Furthermore, we selected leading metabolites based on variable importance in projection scores of > 1.0 and P < 0.05.
RESULTS
Twelve men and six women participated in this study; the participants had a median age of 67.5 years (range, 52–87 years) and were divided into CIN (n = 9) and non-CIN (n = 9) groups. The GC samples exhibited distinct profiles of lysophosphocholine, phosphocholine, phosphatidylethanolamine, phosphatidylinositol, phosphoserine, sphingomyelin, ceramide, and triglycerides compared with their adjacent noncancerous tissues. The glycerophospholipid levels (phosphocholine, phosphatidylethanolamine, and phosphatidylinositol) were 1.4- to 2.3-times higher in the CIN group compared with the non-CIN group (P < 0.05). Alterations in the glycerolipid and glycerophospholipid pathways indicated progression of GC toward CIN.
CONCLUSION
The lipidomics profiles of GC samples were distinct from those of their adjacent noncancerous tissues. CIN status of GC is primarily associated with downstream lipidomics in the glycerophospholipid pathway.
Core tip: We investigated the correlation between comprehensive lipidomic profiles of gastric cancer and the tumor’s chromosomal instability (CIN) status. In this disease landscape study, which involved no pre-specified hypotheses, we combined a gene molecule classification method with a lipidomic method to discover metabolic information for accurate tumor classification. CIN-status-based lipidomics profiling demonstrated translational potential for biomarker discovery and development of novel therapeutic strategies.
