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

doi:10.4251/wjgo.v11.i3.181

Glycerophospholipids pathways and chromosomal instability in gastric cancer: Global lipidomics analysis

World J Gastrointest Oncol. 2019 Mar 15;11(3):181-194. doi: 10.4251/wjgo.v11.i3.181.

Authors

Affiliations

¹ Molecular Medicine Research Center, Chang Gung University, Taoyuan 333, Taiwan.
² Department of Surgery, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan 333, Taiwan.
³ Clinical Metabolomics Core Lab, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan 333, Taiwan.
⁴ Department of Pathology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan 333, Taiwan.
⁵ Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan 333, Taiwan.

Abstract

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.

Keywords: Chromosomal instability; Gastric cancer; Glycerophospholipids; Lipidomics profile; Metabolomics.