The Value Of SNP In LncRNA MEG3 And HOTAIR And Prognostic Nutrition Index(PNI) In Predicting The Sensitivity Of Neoadjuvant Chemotherapy And Prognosis In Locally Advanced Breast Cancer

PART 1 THE VALUE OF SNP IN LNCRNA MEG3 AND HOTAIR IN PREDICTING THE SENSITIVITY OF NEOADJUVANT CHEMOTHERAPY AND PROGNOSIS IN LOCALLY ADVANCED BREAST CANCERObjective To investigate the effect of HOTAIR and MEG3 single nucleotide polymorphism on the sensitivity,prognosis and side effects of neoadjuvant chemotherapy in locally advanced breast cancer.Methods Select the SNP loci of 3 MEG3 genes(rs10132552,rs941576,rs7158663),and the SNP loci of the 4 HOTAIR genes(rs920778,rs1899663,rs7958904,rs12826786),DNA extracted from the whole blood samples of breast cancer patients receiving neoadjuvant chemotherapy before treatment.and SNP genotype analyzed by time-of-flight mass spectrometry.The relationship between MEG3 and HOTAIR genotypes,haplotype and neoadjuvant chemotherapy(p CR)and side effects was analyzed by chi square test and multiple factor Logistic regression model.Survival curve was fitted by Kaplan-Meier method,and survival analysis was carried out by Log-rank test and single factor and multiple factor Cox proportional risk regression model.Results A total of 144 patients were included in this study and were tested for SNP genotype.The 7 SNPs tested were consistent with Hardy-Weinberg equilibrium quantification.As for the curative effect,the CC+TC type of MEG3 rs10132552 is easier to reach p CR than that of the TT genotype(OR=2.396,95%CI 1.202-4.777,p=0.013).The AA+AC type of HOTAIR rs1899663 is easier to reach p CR than that of the CC genotype(OR=2.293,95%CI 1.113-4.723,p=0.024),and the TT+TC type of HOTAIR rs12826786 type is harder to achieve p CR than that of CC(OR=0.436,95%CI 0.212-0.898,p=0.024).In terms of survival,the DFS of the MEG3 rs10132552 TT genotype was poorer than the CC+TC genotype(HR=7.131,95%CI 1.162-43.769,p=0.034);the DFS of the MEG3 rs941576 AG+GG genotype was better than the AA genotype(HR=3.898,95%CI 1.052-14.439,p=0.042);DFS of the MEG3 rs7158663 AA+AG genotype was better than the GG genotype(HR=0.124,95%CI 0.016-0.964,p=0.046).At the same time,the DFS of other haplotypes of MEG3 rs10132552+rs941576 is also better than that of TA haplotype(HR=0.220,95%CI 0.053-0.916,p=0.037).In terms of side effects,HOTAIR rs1899663,HOTAIR rs7958904 and MEG3 rs7158663 GG are independent factors affecting the decline of hemoglobin.Patients with type HOTAIR rs1899663 CA+AA were more prone to hemoglobin decline than those of CC type(OR=4.022,95%CI1.151-14.048,p=0.029);HOTAIR rs7958904 GG was prone to decrease in hemoglobin than CC+CG(OR=0.251,95%CI 0.08-0.784,p=0.017);MEG3 rs7158636 GG was easier than AG+AA to appear to decrease in hemoglobin(OR=0.249,95%CI 0.09-0.684,p=0.007).Conclusion HOTAIR and MEG3 gene SNPs are potential markers for efficacy,prognosis and side effects of neoadjuvant chemotherapy with paclitaxel plus cisplatin.The MEG3 gene SNPs is associated with the efficacy,prognosis and side effects of neoadjuvant chemotherapy for breast cancer.The HOTAIR and MEG3 gene SNPs is associated with the efficacy and side effects of neoadjuvant chemotherapy for breast cancer.PART 2 THE VALUE OF PROGNOSTIC NUTRITION INDEX(PNI)IN PREDICTING THE SENSITIVITY OF NEOADJUVANT CHEMOTHERAPY AND PROGNOSIS IN LOCALLY ADVANCED BREAST CANCERObjective Locally advanced breast cancer has a higher risk of recurrence and metastasis,and a poor prognosis.Neoadjuvant chemotherapy has become a standard treatment for locally advanced breast cancer.Pathological examination is the gold standard for the evaluation of curative effect of neoadjuvant chemotherapy.PNI is associated with the prognosis of a variety of malignant tumors.At present,PNI has little research in the prognosis of breast cancer.The purpose of this study was to explore the role of high or over-high PNI in predicting the efficacy and long-term prognosis of neoadjuvant chemotherapy in patients with a high Prognostic nutritional index(PNI > 45)of locally advanced breast cancer.Methods The present study reviewed the prospective clinical data of patients in clinical trials and included the analysis of women who were diagnosed locally advanced breast cancer with PNI > 45,from October 2013 to November 2016.The relationship between PNI and Pathologic complete response(p CR)was analyzed by Logistic single factor and multiple factor regression,and the survival analysis was carried out by Kaplan-Meier and Cox proportional hazard model.Results A total of 123 patients were enrolled in this study.The median followup time was 24 months.Logistic single factor regression analysis showed that there was a significant correlation between PNI and p CR(OR=0.889,95%CI was 0.801-0.986,p=0.026),and patients with over-high PNI were less likely to reach p CR.In addition,the ER state(OR=0.231,95%CI is 0.102-0.524,P=0.000),HER2 state(OR=2.748,95%CI is 1.380-6.543,P=0.006),and whether high and low levels of Ki67(OR=1.041,95%CI ?1.021-1.061,P=0.000)is related to p CR.Patients with negative ER status,HER2 status and Ki67 > 14% were more likely to achieve p CR.The multiple regression analysis of menstrual state,mass size,ER status,PR status,HER2 status,Ki67,BMI and Logistic found that the PNI and PCR rates were significantly correlated(OR= 0.858,95%CI for 0.750-0.984,p=0.028),and the over-high PNI patients were easier to achieve.In addition,the HER2 state(OR= 4.706,95%CI is 1.658-13.36,P=0.004),Ki67 high and low(OR=1.048,95%CI is 1.022-1.074,P=0.000),BMI index can be predicted.The patients were divided into high PNI group and over-high PNI group by 75% division(PNI=55),and the survival curve of Kaplan-Meier was plotted.The results showed that the two groups had no recurrence survival(relapsefree survival,RFS),and the over-high PNI group was poor in survival(Logrank p=0.0365).The multifactor analysis of the Cox proportional hazard regression model showed that there was significant statistical difference between high PNI and over-high PNI two groups(HR= 6.371,95%CI 1.652~24.57,P= 0.007),and the patients with over-high PNI had worse prognosis.Ki67 high and low levels(HR=1.038,95%CI 1.003-1.076,P=0.035)can also effectively predict RFS,and the prognosis of patients with higher Ki67 is worse.In the HER2 positive subgroup,there was a significant correlation between different PNI and RFS(HR=48.30,95%CI was 1.572-1484.25,P=0.026),and the prognosis of high PNI patients was significantly worse.Conclusion For patients with locally advanced breast cancer with PNI >45,PNI can predict the sensitivity of neoadjuvant chemotherapy and the prognosis.