Expression And Prognosis Of MiR-27a And GATA3 In Invasive Micropapillary Carcinoma Of The Breast

ObjectiveInvasive micropapillary carcinoma(IMPC)is a special subtype of invasive breast cancer,which has biological behaviors such as high lymphatic vessel invasion,high lymph node metastasis,high recurrence and distant metastasis.miRNA is a type of non-coding small RNA,and its abnormal expression is closely related to the occurrence and development of a variety of cancers.The previous study of our group found that the expression of miR-27a was significantly down-regulated in IMPC.Bioinformatics analysis showed that GATA3 is a potential target gene of miR-27.This study examined the expression differences of miR-27a and GATA3 in IMPC and invasive ductal carcinoma not otherwise specified(IDC-NOS),and analyzed their correlation with clinical pathological characteristics and prognosis of patients,and reveal the significance of miR-27a and GATA3 expression in IMPC of the breast.Methods1.The clinical data of 211breast cancer patients underwent surgery in Tianjin Medical University Cancer Institute&Hospital from January 2008 to December 2009were selected,of which 102 were IMPC and 109 were IDC-NOS.Immunohistochemistry was used to detect the difference in expression of GATA3 in IMPC and IDC-NOS,and in situ hybridization was used to detect the difference in expression of miR-27a in IMPC and IDC-NOS.The relationship between miR-27a/GATA3 and clinicopathological characteristics and patient prognosis were analysised by Statistical methods.2.26 samples of IMPC and IDC-NOS fresh tissue samples from March 2019 to April 2019 were selected.Real-time quantitative PCR(RT-q PCR)was used to detect the expression levels of miR-27a and GATA3 in fresh tissues,primary cells and breast cancer cell lines.Results1.IMPC and IDC-NOS tissues have different clinical pathological characteristics.IMPC patients have higher lymph node metastasis positive rate(p<0.01)and higher ER positive rate(p=0.017).In situ hybridization showed that miR-27a expression was low in IMPC tissues,and miR-27a expression was negatively correlated with lymph node metastasis(r_s=-0.228,p=0.021)and tumor stage(r_s=0.256,p=0.009).Immunohistochemical results showed that GATA3 was highly expressed in IMPC tissues.GATA3 expression was positively correlated with lymph node metastasis(r_s=0.230,p=0.022),ER(r_s=0.536,p<0.01)and PR(r_s=0.264,p=0.01)expression,and GATA3 expression was negative correlation with HER2(r_s=-0.251,p=0.010).2.RT-q PCR detected the expression of miR-27a and GATA3 in 13 mixed of IMPC and 13 IDC-NOS fresh tissue samples,it was found that miR-27a was low expressed in IMPC compared with IDC-NOS(p<0.05),GATA3 is highly expressed in IMPC(p<0.05).3.GATA3 is highly expressed in T47D and MCF7 cell lines,low in MDA-MB-231 and SK-BR3 cell lines,and moderately expressed in MCF-10A cell line.T47D and MCF7 cell lines can construct stable GATA3 low expression cell lines,and MDA-MB-231 and SK-BR3 cell lines can construct stable cell lines with high expression of GATA3.miR-27a is highly expressed in MCF-10A cell line,moderately expressed in MDA-MB-231,MCF7 and SK-BR3 cell lines,and lowly expressed in T47D cell line.Stable miR-27a low expression cell line can be constructed with MCF-10A cell line,and stable miR-27a high expression cell line can be constructed with T47D cell line.4.Kepian-Meier survival curve analysis found that the disease-free survival rate(DFS)and overall survival rate(OS)of GATA3 high expression patients were lower than those of GATA3 low expression patients(p=0.026,p=0.013);Patients with high expression of miR-27a had significantly higher DFS(p=0.026)and OS(p=0.008)than patients with low expression of miR-27a.In addition,Cox proportional hazard model analysis showed that GATA3 had no independent prognostic significance for DFS and OS in IMPC patients,and miR-27a expression was independent prognostic factors for DFS(HR=0.812;95%CI:0.043-1.938;p=0.033)and OS(HR=0.738;95%CI:0.560-1.029;p=0.018)in IMPC patients.ConclusionCompared with IDC-NOS,miR-27a is lowly expressed in IMPC tissues,and GATA3 is highly expressed in IMPC tissues.miR-27a and GATA3 are related to lymph node metastasis in breast IMPC patients,and the expression of miR-27a is negatively correlation with GATA3.GATA3 had no independent prognostic significance for DFS and OS in IMPC patients,miR-27a low expression has an adverse effect on the prognosis of IMPC patients,and is an independent prognostic factor for DFS and OS in IMPC patients,and miR-27a is a potential biomarker for breast IMPC.