Published online Sep 7, 2018. doi: 10.3748/wjg.v24.i33.3760
Peer-review started: May 23, 2018
First decision: June 13, 2018
Revised: June 27, 2018
Accepted: July 16, 2018
Article in press: July 16, 2018
Published online: September 7, 2018
To explore the correlation of metabolomics profiles of gastric cancer (GC) with its chromosomal instability (CIN) status.
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.
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.
Metabolomic profiles of GC tumors and the adjacent healthy tissue are distinct, and the CIN status is associated with downstream metabolic alterations in GC.
Core tip: We studied the correlation of the comprehensive metabolomic profiles of gastric cancer with its chromosomal instability (CIN) status. In this disease landscape study with no pre-specified hypothesis, we combined a gene molecule classification method with a metabolomics method to discover metabolic information for accurate tumor classification. CIN status-based metabolomic profiling has demonstrated translational potential in biomarker discovery and novel therapeutics development.