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

World Journal of Gastrointestinal Oncology 2019年第3期11卷 181-194页

作者： 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 Molecular Medicine Research Center Chang Gung University Clinical Metabolomics Core Lab Chang Gung Memorial Hospital at Linkou and Chang Gung University Department of Medical Imaging and Intervention Imaging Core Lab Institute for Radiological Research Chang Gung Memorial Hospital at Linkou and Chang Gung University Department of Surgery Chang Gung Memorial Hospital at Linkou and Chang Gung University Department of Pathology Chang Gung Memorial Hospital at Linkou and Chang Gung University Department of Laboratory Medicine Chang Gung Memorial Hospital at Linkou and Chang Gung University Department of Biomedical Science College of Medicine Chang Gung University

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 *** To explore the associations of CIN with downstream lipidomics *** 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 line, 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 *** 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.

关键词： Chromosomal instability Gastric cancer Glycerophospholipids Metabolomics Lipidomics profile

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Metabolomic alterations and chromosomal instability status in gastric cancer

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World Journal of Gastroenterology 2018年第33期24卷 3760-3769页

作者： 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 Clinical Metabolomics Core Lab Chang Gung Memorial Hospital at Linkou and Chang Gung UniversityTaoyuan 333Taiwan Department of Medical Imaging and Intervention Imaging Core LabInstitute for Radiological ResearchChang Gung Memorial Hospital at Linkou and Chang Gung UniversityTaoyuan 333Taiwan Chang Gung Memorial Hospital at linkou and Chang Gung University Taoyuan 333Taiwan Department of Pathology Chang Gung Memorial Hospital at Linkou and Chang Gung UniversityTaoyuan 333Taiwan Department of Medical Biotechnology and Laboratory Science College of MedicineChang Gung UniversityTaoyuan 333Taiwan Department of Biomedical Science College of MedicineChang Gung UniversityTaoyuan 333Taiwan

AIM To explore the correlation of metabolomics profiles ofgastric cancer(GC) with its chromosomal instability(CIN) *** Nineteen GC patients were classified as CIN and nonCIN 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 chromatographymass 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 line, glutamic acid, oxidized glutathione, succinyladenosine, and uridine diphosphate-Nacetylglucosamine levels, but significantly lower butyrylcarnitine, glutathione hydroxyhexanoycarnitine, inosinic acid, isovalerylcarnitine, and threonine levels(all P line 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 *** Metabolomic profiles of GC tumors and the adjacent healthy tissue are distinct, and the CIN status is associated with downstream metabolic alterations in GC.

关键词： Gastric cancer Metabolomics Oncogene Copy-number Chromosomal instability Liquid chromatography-mass spectrometry

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