Basic Study
Copyright ©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
Processing time: 120 Days and 15.1 Hours
ARTICLE HIGHLIGHTS
Research background

Gastric cancer (GC) leads to worldwide cancer mortality, especially in developing countries. Recently, The Cancer Genome Atlas (TCGA) Research Group proposed an integrative genomic analysis, dividing gastric cancer into four subtypes—Epstein Barr Virus positive, microsatellite unstable, chromosomally instable (CIN), and genomically stable, based on gene expression profiling of the exome sequences, copy-number alterations, gene expression, DNA methylation, and protein activities. 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. Metabolomics, which study the result of the interaction of the biosystem’s genome with its environment and detect the end product of gene expression, offers the opportunity to understand the complex molecular mechanisms and to identify the diagnostic biomarkers of human GC. Although mass spectrometry (MS) and nuclear magnetic resonance system have been used widely to investigate metabolic changes in biological processes, most of those findings were limited to focus on water-soluble compounds, and volatile metabolites. Perturbation of lipid metabolism would also contribute to observing in the cancer progression by detecting the activity of the dysregulated core enzymes in lipid pathways and the global lipid metabolic alterations in cancer metastasis. Global lipidomics provides the most details detection and qualification of the cellular lipids in systems biology. The background, present status, and significance of the study should be described in detail.

Research motivation

In our previous study, metabolomic profiles of GC tumors and the adjacent healthy tissue are distinct, and altered pathways involving amino acid metabolism, glyoxylate and dicarboxylate metabolism. In this study, we hypothesize that lipidomic alternations reflect the CIN or non-CIN status of GC to provide the exploration of the correlation the lipidomic metabolites of GC with its CIN status.

Research objectives

The main objectives aimed to discover the numerous biomarkers from lipidomic studies and explore the associations of CIN with its downstream lipidomics profiles.

Research methods

Tumor samples were categorized as CIN or non-CIN type by the TCGA system. We extracted the genomic DNA, and quantified them for genomic analysis. In total 409 leading oncogenes and tumor suppressor genes in the GC tumor tissue were sequenced. For lipidomic metabolite research, tissue extraction through Folch method and performed profiling using an LC/MS system. Data processing and statistical analysis for lipidomic analysis to discover the potential metabolites using MarkerLynx XS software, SIMCA-P+ and MetaboAnalyst 4.0.

Research results

This study demonstrated the Lipidomic profiling of GC tumors showed distinct profiles in glycerolipid, glycerophospholipid and sphingolipid compared with adjacent non-cancerous tissues. The glycerophospholipid levels (phosphocholine, phosphatidylethanolamine, and phosphatidylinositol) demonstrated a 1.4- to 2.3-fold increase in the CIN group, compared with the non-CIN group (P < 0.05). Alteration of the glycerolipid and glycerophospholipid pathways involved throughout the evolutions of GC formation toward chromosomal instability.

Research conclusions

Lipidomics profiles of GC tumors were distinct against the adjacent non-cancerous tissue. The CIN status of GC primarily associated with the downstream lipidomics in glycerophospholipid pathway.

Research perspectives

Our study provided the genomic classification method and discovered lipidomic information to correlate with its CIN status. To validate our initial findings, more sample collections with longer follow up times will be considered.