Serum metabolomic profiling of human gastric cancer and its relationship with the prognosis.
Serum metabolomic profiling of human gastric cancer and its relationship with the prognosis.
复制标题
人胃癌血清代谢组学分析及其与预后的关系
DOI：
10.18632/oncotarget.21314
复制
发表时间：
2017-12-15
期刊：
影响因子：
--
通讯作者：
Suo J
中科院分区：
文献类型：
--
作者：
Wang D;Li W;Zou Q;Yin L;Du Y;Gu J;Suo J
目的 探讨胃癌（GC）患者血清代谢物及其与GC预后的关系，寻找潜在的GC特异性血清生物标志物。方法采用高效液相色谱-电喷雾/四极杆飞行时间质谱（HPLCESI/Q-TOFMS）技术对我院2008年9月至2009年8月招募的125例单灶GC初期GC患者和38名健康人的血样进行分析。应用主成分分析（PCA）、层次聚类分析、偏最小二乘判别分析（PLS-DA）、多元COX回归分析、方差分析和K-M生存曲线等多种统计方法对获得的原始海量数据进行分析，以分析GC的独立预后因素。通过将 m/z 比和离子模式与 HMDB (www.hmdb.ca) 数据库发布的数据进行比较，确认了这些代谢物的结构。结果通过PLS-DA测试，测试组和验证组中ESI+模式VIP>1的16种血清代谢物均能明确区分GC患者和健康人（p<0.05）。多变量COX回归分析显示TNM分期、2,4-己二烯酸、十二烷酸4-甲基苯基酯和三丁酸甘油酯是GC的独立预后因素（p<0.05）。 K-M生存分析中，所选3种血清代谢物联合或单独使用的高水平组的生存率显着低于低水平组（p<0.05）。结论 血清2,4-己二烯酸、十二酸4-甲基苯基酯和三丁酸甘油酯低水平可能是GC的重要独立预后因素。
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.