The Relations Of The Efficacy Of Therapy Strenthing Healthy Energy In Patients Who Treated With Neoadjuvant Chemotherapy With Metabolomics Analysis

ObjectiveThe study is to observe if the Therapy Strenthing Healthy Energy would emphasize the efficacy of neoadjuvant chemotherapy in patients who are diagnosed with breast cancer. By the way metabolomics will be used to make dynamic description what will change in the body after chemotherapy. We can further explore the correlation between the efficacy of chemotherapy and the change of metabolomics. In this case,we are able to predict the efficacy of chemotherapy.MethodsProspective randomized controlled study was conducted. The patients who meet the criteria that have been diagnosed with breast cancer and planed to have neoadjuvant chemotherapy.will be divided into two groups:treatment group (neoadjuvant chemotherapy+SFI) and control group (neoadjuvant chemotherapy alone),with 17 and 18 patients in each group, neoadjuvant chemotherapy (chemotherapy programs include:TEC, EC-T (H), TCH, FEC-T,21 days/cycle, a total of 3 cycles (dose reference:NCCN breast Cancer clinical Practice Guidelines. v.2013) were all given to the two groups, with Shenqifuzheng Injection added to the treatment group (sig:250ml. qd. ivd. Dayl-6 in each chemotherapy cycle);On the other hand, plasma and morning urine specimens of every patients were kept for metabolomics analyzes on one day before the first cycles and the tenth day after the third cycle. The evaluation of chemotherapy efficacy were made after the three cycles, the ratio of the patients who got CR (complete response) or PR (partial response) and all of the patients. The ultra high-performance liquid chromatography mass spectrometry (UPLC/Q-TOF MS) was used for metabolomics analysis of plasma and morning urine; Analyte software was used to get metabolic profiling pattern before and after chemotherapy in control group and treatment group respectively; MarkerView4.1 software was used for merging metabolic fingerprint chromatographic, peak identification, peak alignment and data preprocessing, such as normalization, and so on. The pretreated data were analyzed points using partial least squares discriminant analysis (PLS-DA) and consensus orthogonal partial least squares discriminant analysis (OPLS-DA), to compare the content of special metabolites of plasma and urinary respectively between the two groups. According to the VIP value of OPLS-DA (VIP value> 1.85), considering of biological significance of each compound, we could filter some small compounds in the body which made greater contribution to classify each groups, and then searched the HMDB database with the matching isotope mass spectrometry for a compound which might affect the efficacy of chemotherapy and show as an indentified marker.Results1.Clinical efficacy:The treatment group and control group each had a response rates:58.8%(10/17) VS 50.0% (9/18), respectively. The former one was slightly better than the latter one, however the difference was not statistically significant (P> 0.05);2. Metabolomic analysis:(1)the plasma metabolomic analysis showed that: the metabolomic pattern was significantly different after chemotherapy in the two groups. A total of 13 metabolites changed obviously before and after chemotherapy, but the extent of the changes in two groups were inconsistent, in which hydroxy pyruvate phosphate, stearic acid,β-tocopherol, palmitic acid amide, calciferol, Myrigalone E, ubiquinone 4, alpha CEHC reduced after chemotherapy in two groups(P<0.05);tricosanoic acid, ceramide raised after chemotherapy than before (P<0.05); vitamin K2, umbel liferone decreased after chemotherapy in the control group (P<0.05), but almost no change in the treatment group (P> 0.05). These compounds react in some metabolic pathway including amino acids pathway, lipids pathway, fatty acids pathway and vitamin pathway. (2) Morning urine metabolomic analysis showed that:the metabolomic pattern was significantly different after chemotherapy in the two groups. A total of 10 metabolites changed obviously before and after chemotherapy but the extent of the changes in two groups were inconsistent,in which Palm amides, creatinine increased after chemotherapy in the two groups (P<0.05); lysophospholipids, lysolecithin P, stearic acid amide (eighteen amide), chenodeoxycholic acid, ubiquinone 4 decreased after chemotherapy (P<0,05); indomethacin glutamine increased after chemotherapy in the control group (P <0.05), but no significant change in the treatment group(P> 0.05); 5-hydroxy indole acetic acid and 1-(propanediamino) cyclopropanecarboxylate had no significant change in the two groups after chemotherapy (P> 0.05). Similar to plasma metabolomics, the characteristic compounds in the morning urine react in some metabolic pathway including amino acids pathway, lipids pathway, fatty acids pathway and energy metabolism pathway.Conclusion1. Shenqifuzheng Injection does not make neoadjuvant chemotherapy more efficient obviously.2. Shenqifuzheng Injection may improve the chemotherapy-induced metabolic disorders of human internal environment, which inplies that The Therapy Strenthing Healthy Energy may have a positive effect on improving the efficacy of chemotherapy.