Metabolomic alterations and chromosomal instability status in gastric cancer

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*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

22 Scopus citations

Abstract

AIM To explore the correlation of metabolomics profiles of gastric cancer (GC) with its chromosomal instability (CIN) status. METHODS Nineteen GC patients were classified as CIN and non- CIN 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 chromatographymassspectrometry. 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. RESULTSIn 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 theCIN 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 lowerbutyrylcarnitine, glutathione hydroxyhexanoycarnitine,inosinic acid, isovalerylcarnitine, and threonine levels(all P < 0.05). CIN tumors contained significantlyhigher 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, andtryptophan biosynthesis. CONCLUSIONMetabolomic profiles of GC tumors and the adjacenthealthy tissue are distinct, and the CIN status isassociated with downstream metabolic alterations in GC.

Original languageEnglish
Pages (from-to)3760-3769
Number of pages10
JournalWorld Journal of Gastroenterology
Volume24
Issue number33
DOIs
StatePublished - 07 09 2018

Bibliographical note

Publisher Copyright:
© The Author(s) 2018.

Keywords

  • Chromosomal instability
  • Copy-number
  • Gastric cancer
  • Liquid chromatography-mass spectrometry
  • Metabolomics
  • Oncogene

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