Preliminary Study On The Mechanism Of PIK3CA Gene Mutation In The Development And Progression Of Breast Cancer

Backgound:pik3ca gene is a common mutant gene in breast cancer.Mutation of pik3ca gene can cause activation of PI3K/AKT/mTOR pathway,which leads to the rapid proliferation,invasion and metastasis of breast cancer cells.pik3ca gene mutation may be related to the prognosis of breast cancer patients.This study was to investigate the relationship between the mutation of pik3ca gene and the development and prognosis of breast cancer in Yunnan,which will provide a theoretical basis for the individualized treatment of breast cancer patients in Yunnan.Objective:Reveal the relationship between pik3ca gene mutation and the development and prognosis of breast cancer.Methods:The pik3ca gene mutation was detected by DNA sequencing in patients with breast cancer in Yunnan Province.The expression of pik3ca signaling pathway protein was detected by immunohistochemistry and immunoblotting.Comprehensive analysis of meta-analysis of pik3ca gene mutation and prognosis of breast cancer.Results:?The meta-analysis showed that the pik3ca gene mutation was associated with the progression-free survival of patients with Her2-overexpression breast cancer(HR = 1.52,95%Cl:1.04-2.21,P=0.029)with trastuzumab targeting therapy.pik3ca mutations were not associated with the overall survival of OS(HR=1.31,95%Cl:0.63-2.72,p= 0.470)in Her2-overexpression breast cancer treated with trastuzumab.At the same time,mutations in the pik3ca gene were not associated with trastuzumab targeting Her2-overexpression breast cancer(OR = 0.67,95%Cl:0.32-1.40,p = 0.292).The data analysis in the TCGA database also indicated that the mutation of the pik3ca gene was not associated with survival in patients with breast cancer(p>0.05),PI3K(p110a),pik3ca gene expression was not associated with survival in breast cancer patients(p = 0.36033>0.05);?The proportion of Her2-overexpression was 46%in breast cancer patients,6%,8%and 40%in the remaining Luminal A,Luminal B and Basal-like respectively;?There was no correlation between the mutations of exon 9 of pik3ca gene and the molecular classification of breast cancer(p = 0.946),lymph node metastasis(p =0.142),and PI3K expression(p= 0.963),but there exist significantly relationship between exon 9 of pik3ca mutation and malignancy(p = 0.005);?The expression of PI3K(p110a),PR,ER,Her2,Ki67,P53,Bcl2 and MMP9 was not statistically significant(p>0.05)in breast cancer with lymph node metastasis or breast cancer malignancy;?The PI3K/AKT/mTOR pathway in the MDA-MB-231 cells was not activated,and the PI3K/AKT/mTOR pathway in the other four cells was activated at a certain level,and the activation of PI3K/AKT/mTOR pathway in Her2-amplified SK-BR-3 cells was the most significant.The expression of p-P70S6,p-4EBP1(p37)and p-4EBP1(ser65)were not the same,and the expression of p-P70S6 in MCF-7 was the most significant,and the expression of p-4EBP1 in T47D cells(T37/46)and p-4EBP1(ser65)were the most significant.In addition,the MEK/ERK pathway of five breast cancer cells was activated to a certain extent,and the activation of MEK/ERK pathway in MDA-MB-231,MDA-MB-468 and SK-BR-3 cells was significantly higher than that The remaining three cells;Conclusion:The data in the TGCA database showed that the mutation of pik3ca and the expression of pik3ca were not related to the prognosis of breast cancer patients.However,the meta-analysis showed that the mutation of pik3ca gene was associated with the progression-free survival of Her2-overexpression breast cancer patients with trastuzumab-based therapy.Therefore,pik3ca gene mutation may be related to breast cancer prognosis,which needs our further study.Breast cancer samples concentrate on LuminalB classification.The positive expression rate of P53 and PTEN which are tumor suppressor genes is low.The positive expression of Bcl2 which is anti-apoptotic,and the positive expression of MMP9 which is associated with cell invasion,and the positive expression of PI3K(p110a)which can activate cell proliferation is higher.There were E545K and s553fs*7 mutations in exon 9 of pik3ca gene in breast cancer samples,and there was no mutation of E545A of pik3ca gene.There was no correlation between the mutations of exon 9 of pik3ca gene and molecular classification or lymph node metastasis or the expression of PI3K(p110a)protein.The activation of PI3K/AKT/mTOR pathway was observed in MCF-7,T47D,MDA-MB-468 and SK-BR-3 cells.In addition,the activation status of Basal-like MDA-MB-231 and MDA-MB-468 MEK/ERK pathway was significantly higher than other types of cells,which Suggests the activation of the MEK/ERK pathway can be used as a key to the regulation of Basal-like cell proliferation.