The Value Of MRI,WES,RNA-seq In Predicting The Efficacy Of Neoadjuvant Chemotherapy For Breast Cancer

Objective: To Explore the value of MRI multi-parameter imaging,whole exon sequencing and RNA-seq in predicting the efficacy of neoadjuvant chemotherapy for breast cancer.Methods: It was a prospective,nonrandomized,monocentric study.A total of 42 breast cancer patients were enrolled.The breast MRI-DWI-IVIM imaging was performed before chemotherapy,after one cycle of chemotherapy,after two cycles of chemotherapy,and before surgery.The values of multi-parameters of breast magnetic resonance were collected in different treatment time periods,including apparent diffusion coefficient(ADC),true diffusion coefficient(slow ADC),pseudo diffusion coefficient(fast ADC)and perfusion fraction(f).In addition,before neoadjuvant chemotherapy,fresh cancer tissue samples were collected for whole exome sequencing and transcriptome sequencing.According to the postoperative pathological results,patients were divided into pathological complete remission(pCR)group and nonpathological complete remission(non-pCR)group.Through statistical and bioinformatics analysis methods explored the value of MRI,WES and RNA-seq in predicting the efficacy of neoadjuvant chemotherapy for breast cancer.Results: A total of 42 patients were enrolled,of which 37 patients were included in the final imaging analysis,25 patients were included in the WES analysis,and 22 patients were included in the RNA-seq analysis.Analysis of magnetic resonance data of 37 breast cancer patients found that: At the end of the first cycle of neoadjuvant chemotherapy,the slow ADC value in the pCR group was significantly higher than that in the non-pCR group(P<0.05).At the end of the second cycle of neoadjuvant chemotherapy,the slow ADC and fast ADC values of the pCR group were significantly higher than those of the non-pCR group(P<0.05).Multivariate Cox regression analysis showed that the increase of fast ADC2 value was a risk factor in the process of neoadjuvant chemotherapy(P<0.05)in pCR(HR=1.027,95%CI: 1.003～1.052).The analysis of WES data from 25 breast cancer patients before treatment found that the mutation types of tumor samples in the pCR group and the non-pCR group were basically the same.The DDX11 mutation frequency was the highest in the pCR group(60%),and the PIK3 CA and TP53 mutation frequency was the highest in the non-pCR group(55% and 50%).There are differences in ZNF716 and RBMXL2 gene mutations between the pCR and non-pCR groups(P<0.05).Compared with the pCR group,the PIK-AKT pathway-related gene mutation rate is higher in the non-pCR group(20% vs70%),in the pCR group,the copy number variation was more stable,while in the nonpCR group,the copy number variation showed obvious amplification and deletion.Analysis of the differential expression of RNA-seq before treatment in 22 patients found that compared with the non-pCR group,TNFSF11,VSTM5,PGM5P2 and other genes were up-regulated in the pCR group,and SERPINE1,COMP,CNTNAP2 and other genes were down-regulated,and genes related to metabolic pathways are upregulated,and genes related to PI3K-AKT signaling pathways are down-regulated.Conclusion: Early rise of slow ADC and fast ADC in neoadjuvant chemotherapy for breast cancer is associated with pCR.Mutations in ZNF716 and RBMXL2 genes can help predict the outcome of neoadjuvant chemotherapy.Patients with mutations in genes related to the PIK-AKT pathway are more difficult to achieve pCR.The upregulation of genes related to metabolic pathways and the down-regulation of PI3K-Akt signaling pathway are related to the pathological outcome of neoadjuvant chemotherapy patients,providing new clues for the treatment and prognosis of breast cancer.