Metabolomic Study On The Sensitivity Of Chemotherapy In The Conversion Treatment Of Gastric Cancer

Objective:The liquid chromatography mass spectrometry(LC-MC)was used to detect the serum of patients with the stage IV and III gastric cancer who received preoperative chemotherapy,to analyze the differences in metabolites between patients with different sensitivity of preoperative chemotherapy,and then to find out the potential biological markers to predict the sensitivity of preoperative chemotherapy for gastric cancer.Method:1.Experimental grouping: The patients were divided into sensitive group(CR or PR)and nonsensitive group(SD or PD)according to sensitivity of preoperative chemotherapy for gastric cancer.2.Sample processing: The sample was taken out at room temperature and thawed.Then,acetonitrile was added and high-speed centrifugation(14000 rpm,5 min)was performed.The supernatant was collected for analysis by high performance liquid chromatography mass spectrometry.3.Chromatographic analysis and data processing: Serum samples were detected by liquid chromatography-mass spectrometry to obtain a metabolite profile between the sensitive group and nonsensitive group.The Marker View software was used to analyze the primary data,such as principal component analysis,t-test,and discriminant analysis,to find the important metabolites between the sensitive group and the nonsensitive group.The results were analyzed by cluster analysis and ROC curve to select metabolites with the discriminatory ability.And then the metabolites was used to separate the dependent group for the observation of the discriminatory ability for patients with different sensitivity of preoperative chemotherapy.Result:In the positive and negative ion modes,from serum total ion chromatogram which is obtained from the Peakview software,we can clearly observe the differences of samples metabolites of two groups;The PCA scores showed that the patients in the sensitive group and nonsensitive group could be well separated.We selected 319 metabolites with P<0.05 including 255 in positive ion mode and 64 in negative ion mode by t-test;SVM discriminate analysis was used to select 7 important metabolites.Finally,cluster analysis and ROC curves were drawn to select 4 metabolites with good discriminatory ability.These 4 metabolites was used to separate the dependent group for the observation of the discriminatory ability for patients with different therapeutic efficacy.The metabolites has good ability to discriminate the serum of the two groups of patients,and may become a potential biomarker for predicting the clinical efficacy of chemotherapy in gastric cancer patients.Logistic regression analysis showed that Deoxyribose 1-phosphate and S-Lactoylglutathione independent influencing factors of chemotherapy sensitivity in the conversion treatment of gastric cancer.Conclusion:Deoxyribose 1-phosphate and S-Lactoylglutathione are independent influencing factors of chemotherapy sensitivity in the conversion treatment of gastric cancer,and may be potential biomarkers of preoperative chemotherapy sensitivity for gastric cancer.