Exploration Of The The Role And Significance Of Multiple Myeloma By Metabolic Biomarkers Using GC-MS

PART ? Exploration of the role and clinical significance of metabolic markers in newly diagnosed multiple myeloma[Objective]To explore diagnostic metabolic biomarkers and pathways for multiple myeloma.[Methods]GC-MS was employed to analyze serum samples from 86 patients with multiple myeloma and 53 healthy controls collected in the First Affiliated Hospital of Soochow University from August 2016 to October 2017.The relative standard deviation(RSD)of quality control(QC)samples was employed to validate the stability of GC-MS approach.86 MM patients and 53 healthy controls were divided into training and test sets.The training set included 18 MM patients and 18 healthy controls.Some other samples entered the test set.Differential metabolites between MM patients and healthy people were screened by partial least squares discriminant analysis(PLS-DA)and t-test with FDR correction in the training set.Next,the method of receiver's working curve(ROC)was applied to validate the selected metabolites in test set.Metabolic pathways were explored by MetPA(Metabolomics Pathway Analysis).[Results](1)A total of 86 MM patients,including 55 male and 31 female,were involved in this study.The median age was 60 years old(38-83 years old).There were 50 cases of IgG type,16 cases of IgA type,1 case of IgD type,1 case of IgM type,3 cases of non-secreted type,and 14 cases of light chain type including 5 cases of kappa light chain type,9 cases of lambda light chain type and 1 case of missing data.(2)In order to verify the reproducibility of GC-MS experimental data.Quality control(QC)samples were uesd and the results showed that the proportion of compounds with the relative standard deviation(RSD)of the relative content of derivatives less than 15%was 77.3%,which implies that the experimental data were reliable.(3)There was a total of 18 metabolites screened by the PLS-DA and t-test FD R correction method compared with the healthy control group.Serum elevating subs tance in MM patients:myo-inositol,L-aspartic acid,glycolic acid,urea,L-phenylalanine,L-proline,9-octadecenoic acid.A substance lowering serum levels:citric acid,malic aci d,pyruvate acid,asparagine,myristic acid,maltose,palmitic acid,stearic acid,L-hydroxypro line,glycerol,?-alanine.(4)Metabolic pathways related to MM differences metabolites involved by MetP A network analysis suggest that patients with MM metabolic disorders are mostly a bout arginine and proline metabolism,alanine,aspartate and glutamate metabolism,pa ntothenate and CoA biosynthesis,aminoacyl-tRNA biosynthesis,citrate cycle(TCA cyc le),beta-alanine metabolism,phenylalanine metabolism,glycolysis or gluconeogenesis,py ruvate metabolism,glycerolipid metabolism,propanoate metabolism,inositol phosphate metabolism,butanoate metabolism(impact>0.05,-Log(p)>1).(5)The 18 metabolites screened in the training set were verified in the test set,and 10 metabolites were identified,which were pyruvate acid,glycolic acid,malic acidL-hydroxyproline,asparagine,citric acid,palmitic acid,myo-inositol,stearic acidmyristic acid(AUC>0.6,p<0.05).[Conclusion]Compared with normal people,some metabolites were significantly changed in newly diagnosed multiple myeloma patients.PART ? Exploration of the metabolic changes associated with the curative effect of multiple myeloma[Objective]To find the metabolites associated with the curative effect of multiple myeloma.[Methodology]We followed 41 newly diagnosed MM patients,all patients received more than 4 courses of treatment and we evaluated the efficacy at the end of follow-up;we devided the 41 patients into two groups(CR+VGPR vs PR+MR+SD),and compared metabolites before and after treatment in patients with better curative effect(CR+VGPR)and poor curative effect(PR+MR+SD)by paired t-test.[Results](1)In 41 patients with MM after treatment,induction chemotherapy was performed in 1 case of DVD,1 case of RD,2 cases of CRD,and 37 cases of PD(including PAD,PTD,PD).Among them,14 patients achieved complete remission(CR),16 patients achieved very good partial remission(VGPR),9 patients had partial remission(PR),1 patient had minimal remission(MR),1 patient had stable disease(SD).The follow-up time of 41 patients with MM was as of October 12,2018,and the median follow-up time was 22.83 months(1.7?34.73 months).The overall 2-year survival rate was 85.5%.(2)We compared the changes of metabolites before and after treatment in 41 patients,most of the marker metabolites at the time of diagnosis changed in the opposite direction to the initial state after treatment.The reduction of urea and the increase of asparagine,palmitic acid,and stearic acid were statistically different.The changes of marker metabolites before and after treatment in different therapeutic groups were further compared.In the better curative group(CR+VGPR),the reduction of urea and increase of malic acid,asparagine,palmitic acid,and stearic acid were statistically significant.In the poor curative effect(PR+MR+SD),there was no significant difference in the substance before and after treatment.[Conclusion]Changes of differential metabolites after treatment in MM patients may suggest different effects.Metabolites can be used as biomarker for the evaluation of the efficacy.