Association Of Expression Of MTFR2 With Prognosis Of Patients With Breast Cancer

Background.Breast cancer has become the second cancer with high incidence and mortality in the world.Despite the molecular detection of estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor-2(HER2)have been widely used and improved the survival of patients in recent years,the clinical outcomes of breast cancer is still relatively poor.Therefore,it is particularly important to explore new molecules which can effectively predict the occurrence,development or prognosis of breast cancer.Mitochondria is related to the multiple stages of malignant tumor.Studies have found that many nuclear genes which can affect the development of malignant tumors by regulating mitochondrial function.Current studies have found that mitochondrial fission regulator 2(MTFR2)can regulate the expression of dual specificity protein kinase TTK(TTK)by activating transcription of promoter,thus affecting the occurrence and therapy of glioblastoma.Therefore,we studied the expression and clinical significance of MTFR2 in breast cancer.Methods: We collected 139 patient samples which were surgically removed and pathologically confirmed as breast cancer in Yantai Yuhuangding Hospital affiliated of Qingdao University.The data included operation age,clinical stage,lymph node status,distant metastatic,ER expression,PR expression,HER2 expression,molecular subtypes status and the time of recurrence and overall survival.Immunohistochemical(IHC)method was used to detect the expression of MTFR2 in breast cancer tissues.The relationship between MTFR2 expression and clinicopathological characteristics were analyzed by the Chi-square test and Fisher's exact test.The correlation coefficient of Spearman was used to further analyze the binary correlation between variables.The recurrence free survival(RFS)and overall survival(OS)were analyzed by the Kaplan–Meier method and the Cox multivariable proportional hazard model.Results:(1)MTFR2 expression was found in the cytoplasm of breast cancer cells,it was difficult to detect in normal breast tissue or adjacent non-cancerous tissue.(2)MTFR2expression were no significant correlation with age(P=0.800),ER expression(P=0.527)and PR expression(P=0.743),respectively.However,MTFR2 expression were significantly associated with clinical stage(P<0.001),T classification(P=0.005),N classification(P=0.001),distant metastatic(P=0.022),HER2 expression levels(P<0.001)and molecular subtypes(P=0.002),respectively.Moreover,Spearman correlation analysis showed that the correlation between MTFR2 expression and clinical stages(r=0.417,P<0.001),T classification(r=0.261,P=0.002),N classification(r=0.312,P<0.001),distant metastatic(r=0.195,P=0.028),and HER2 expression(r=0.297,P<0.001),respectively.(3)Comparedwith low MTFR2 expression,patients with higher expression of MTFR2 exhibited significantly shorter RFS and OS(P<0.001).Both univariate and multivariate survival analyses showed that MTFR2 was an independent prognostic factor for RFS(HR,2.819,95%CI,1.214-6.547,P=0.016)and OS(HR,2.603,95%CI,1.055-6.20,P=0.038)in breast cancer patients.(4)Among HER2 positive subtypes,MTFR2 expression was an important molecule in predicting both RFS(HR,7.927,P=0.045)and OS(HR,7.686,P= 0.049).For triple-negative breast cancer(TNBC)subtypes,MTFR2 was an important molecule for prediction of RFS(HR,6.331,P=0.045)and OS(HR,10.346,P=0.044).Conclusions:(1)The MTFR2 is highly expressed in breast cancer tissue,suggesting that MTFR2 may be helpful for the early diagnosis of breast cancer.(2)MTFR2 expression were statistical significant with clinical stage,T classification,N classification and distant classification,suggesting that up-regulation of MTFR2 is related to the progression of breast cancer.In addition,the expression of MTFR2 is closely related to the expression of HER2,suggesting that it may be a beneficial supplement to targeted therapy for breast cancer.(3)High MTFR2 expression was associated with poor prognostic in breast cancer patients,and such an association is more pronounced in the patients with aggressive tumors(HER2positive and TNBC subtypes).Thus,MTFR2 might serve as a potentially valuable of early diagnosis,prognostic biomarker and clinical target for patients with breast cancer.