Effect And Serum Proteomic Dynamic Analysis Of Feitai Capsule With Maintenance Therapy In Advanced Non-small-cell Lung Cancer Patients With The Syndrome On Deficiency Of Vital Energy And Phlegm Blood-stasis

Objective:1 ) To evaluate the quality of life and progression-free survival of Traditional Chinese Medicinal Compound Feitai Capsules with maintenance therapy in patients with advanced non-small-cell lung cancer.2 ) To analyze the characteristic of serum proteins of the syndrome on deficiency of vital energy and phlegm blood-stasis(SDVEPB) in non-small-cell lung cancer(NSCLC) by SELDI-TOF-MS and bioinformatics methods.Methods:sixty-two patients of SDVEPB in NSCLC were randomly assigned to two groups, the 31 patients in the treatment group with Feitai Capsules,31 in the control group with continual observation.Symptom responses,KPS,quality of life and progression-free survival were evaluated regularly.Variations of the clinical features,symptom responses,KPS,QoL scores were assessed by the analysis of ANOVA,non-parametric tests and the analysis of covariance,PFS by Kaplan-Meier analysis.Surface enhanced laser desorption ionization time of flight mass spectrometry(SELDI-TOF-MS) technology was used to analyze serum samples including 30 cases of SDVEPB in NSCLC patients before treatment,4 weeks after treatment and 7 cases of healthy controls.Protein profiles were generated using IMAC3 protein chips. Biomarker Pattern Software(BPS) was used to detect the protein peaks significantly different between SDVEPB with NSCLC patients and healthy controls.And then established a diagnostic pattern.Results:1) Of the 62 initial cases,there were two dropouts and 60 evaluable cases.The baseline characteristics of the two groups were similar.(P＞0.05).2) Pre-Treatment domain,the physical energy level had been raised at 36.6%(Z= -2.632, P=-0.008) and 26.7%(Z=-2.182,P=-0.029) in Post-Treatment domain in treatment group. There was positive correlation between these two factors(r=0.917,P＜0.001).The treatment group had a significantly improved quality of life and progression-free survival compared to the control group(P=0.048).3) A total of 180 efective protein peaks were detected at the molecular range of 1.0 to 10 ku, among which 83 serum proteins screened respectively(P＜0.05).The decision tree model for differentiating SDVEPB with NSCLC patients from healthy subjects was M/Z 3320.54,with 91.89%accurate.Significantly different protein peaks were found in serum samples of NSCLC patients with different pathological types,clinical stages and smoking history. significantly highly protein peaks were identified in smoking history serum samples with the relative molecular weights of 3009.87Da,3222.21Da,3679.55Da;the relative molecular weights of 1023.84 Da,1026.04 Da,1038.65 Da,1058.25 Da,1075.99 Da,1079.56 Da, 1099.55 Da,1103.95 Da,1106.40 Da,1109.12 Da,1557.443 Da,2123.47 Da,2139.75 Da, 33631.66 Da in squamous cell carcinoma serum samples;and the relative molecular weights of 1189.78Da,1247.72Da,1250.71Da,2392.15Da,3093.49Da in stageⅢserum samples4) A significantly up-regulated protein peaks was identified in posttherapy serum samples with the relative molecular weights of 4877.31Da(P＜0.05).Conclusions:1) Maintenance treatment by Feitai Capsules can effectively improve quality of life and prolongate progression-free survival in patients with advanced non-small cell lung cancer. Suggesting Feitai Capsules may cure SDVEPB in NSCLC patients by regulating protein expression.Further study on the discovered protein-marker may lead to find treatment-related protein target.It is worth to depth studying.2) SELDI-TOF-MS technique combined with decision tree model can help to identify serum proteomic biomarkers related to SDVEPB in NSCLC and the predictive models can discriminate Chinese Medicine diagnostic model of diseases.There was significantly different protein peak in sera of NSCLC patients with different pathological types,clinical stages and smoking history.