Metabolomic alterations and chromosomal instability status in gastric cancer.
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 chromatography-mass 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-N-acetylglucosamine 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.
['Tsai|Cheng-Kun|CK|', 'Yeh|Ta-Sen|TS|', 'Wu|Ren-Chin|RC|', 'Lai|Ying-Chieh|YC|', 'Chiang|Meng-Han|MH|', 'Lu|Kuan-Ying|KY|', 'Hung|Cheng-Yu|CY|', 'Ho|Hung-Yao|HY|', 'Cheng|Mei-Ling|ML|', 'Lin|Gigin|G|']
D000368:Aged D000369:Aged, 80 and over D043171:Chromosomal Instability D005260:Female D016147:Genes, Tumor Suppressor D006801:Humans D008297:Male D053858:Metabolic Networks and Pathways D055432:Metabolomics D008875:Middle Aged D009154:Mutation D011446:Prospective Studies D013270:Stomach D013274:Stomach Neoplasms
Metabolomics Chromosomal instability Gastric cancer Oncogene Liquid chromatography-mass spectrometry Copy-number