Metabolomic alterations and chromosomal instability status in gastric cancer  

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 

机构地区：[1]Clinical Metabolomics Core Lab,Chang Gung Memorial Hospital at Linkou and Chang Gung University,Taoyuan 333,Taiwan [2]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 [3]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 Medical Biotechnology and Laboratory Science,College of Medicine,Chang Gung University,Taoyuan 333,Taiwan [6]Department of Biomedical Science,College of Medicine,Chang Gung University,Taoyuan 333,Taiwan

出　　处：《World Journal of Gastroenterology》2018年第33期3760-3769,共10页世界胃肠病学杂志（英文版）

基　　金：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

摘　　要：AIM To explore the correlation of metabolomics profiles ofgastric cancer(GC) with its chromosomal instability(CIN) status.METHODS 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 < 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-Nacetylglucosamine 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.AIM To explore the correlation of metabolomics profiles ofgastric cancer(GC) with its chromosomal instability(CIN) status.METHODS 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 < 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-Nacetylglucosamine 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.

关 键 词：GASTRIC cancer Metabolomics ONCOGENE COPY-NUMBER CHROMOSOMAL instability Liquid chromatography-mass SPECTROMETRY 

分 类 号：R57[医药卫生—消化系统]