Serum metabolomic profiling of human gastric cancer and its relationship with the prognosis

Abstract

Objective: This study was aimed to investigate serum metabolites in gastric cancer (GC) patients and their relationships with the prognosis of GC in order to find potential specific serum biomarkers for GC.

Methods: Blood samples of 125 GC patients of unifocal GC at initial stage and 38 healthy people recruited in our hospital from September 2008 to August 2009 were analyzed by using high performance liquid chromatography coupled with electrospray ionization/quadrupole-time-of-flight mass spectrometry (HPLCESI/Q-TOFMS). Multiple statistical methods like principal component analysis (PCA), hierarchical clustering analysis, partial least squares discriminant analysis (PLS-DA), multivariate COX regression analysis, variance analysis and K-M survival curve were applied to analyze the raw obtained mass data in order to analyze the independent prognostic factors of GC. The structures of these metabolites were confirmed by comparing the m/z ratio and ion mode of with the data published from HMDB (www.hmdb.ca) databases.

Results: By PLS-DA test, 16 serum metabolites in ESI⁺ mode of VIP>1 in both test group and validation group could definitely distinguish GC patients from healthy peoples (p<0.05). Multivariate COX regression analysis showed TNM staging, 2,4-hexadienoic acid, 4-methylphenyl dodecanoate and glycerol tributanoate were independent prognostic factors of GC (p<0.05). In the K-M survival analysis, the survival rate in high level group of the 3 selected serum metabolites together or alone was significant lower than in those in low level group (p<0.05).

Conclusion: Low serum levels of 2,4-hexadienoic acid, 4-methylphenyl dodecanoate and glycerol tributanoate may be important independent prognostic factors of GC.