Expresssion And Clinical Significance Of MTDH And AKT In Locally Advanced Triple Negative Breast Cancer

Objective: Triple negative breast cancer(TNBC)is considered to be the most aggressive breast cancer subtype with the worst prognosis and no effective targeted therapies,which seriously threatens the life and health of woman.Studies have proved that MTDH(Metadherin)?AKT(also known as protein kinase B,PKB)are highly expressed in various cancers,leading to tumor invasion,metastasis and drug resistance.The PI3K/AKT signal pathway plays an important role in the development and progression of triple-negative breast cancer.However,the relationship between the activation of MTDH/PI3K/AKT signaling pathway and the response of neoadjuvant chemotherapy and prognosis in patients with locally advanced triple-negative breast cancer is not yet clear.Therefore,the data of 41 patients with locally advanced triple negative breast cancer who were diagnosed and treated with neoadjuvant chemotherapy in the Breast Center of the Fourth Hospital of Hebei Medical University from 2013 to 2017 were rearranged and followed up.The expression of MTDH and AKT in breast cancer tissues before neoadjuvant chemotherapy was detected by immunohistochemistry,and the relationship between the expression of MTDH,AKT and the prognosis of locally advanced triple negative breast cancer was discussed in order to providing clinical basis for targeted treatment and prognosis prediction of locally advanced triple negative breast cancer.Materials and Methods: A total of 41 patients with locally advanced triple negative breast cancer who were diagnosed in the Breast Center of the Fourth Hospital of Hebei Medical University from January 2013 to December 2017 were selected.All patients were given neoadjuvant treatment.The expression of MTDH,AKT in breast cancer tissues was detected by immunohistochemistry before neoadjuvant therapy,and retrospectively analyzed the clinical and pathological data including age,menopausal status,tumor size,TNM stage,pathological type,histological grade,chemotherapy rigemens,bp CR or not,number of lymph node metastasis,MP grades.The disease-free survival(DFS)and overall survival(OS)were obtained by telephone follow-up or outpatient reexamination,average follow-up 37 months.The count data was expressed by percentage,and the measurement data was expressed by mean � standard deviation.Spearman correlation analysis was used to explore the correlation between the expression levels of MTDH and AKT.Kaplan Meier was used to draw the survival curve,and Log-rank test was used to compare the survival rate curves.Using Cox univariate and multivariate analysis to analyze the factors influencing the prognosis of locally advanced triple negative breast cancer.Results:1.The relationship between the expression of MTDH and AKT and the clinicopathological features: The high expression of MTDH and AKT was found in the patients of TNM stage III,Ki-67 > 30%,non bp CR,MP1-3 and histological grade 2-3;2.Among 41 cases of locally advanced triple negative breast cancer,24 cases(58.5%)had high expression of MTDH,and the expression of MTDH was significantly related to DFS.DFS in patients with high expression of MTDH was significantly shortened by 17.9 months(43.9 months vs.61.8 months,P = 0.045).There was no significant difference in OS between MTDH high expression group and low expression group(53.2 months vs 64.6 months,P = 0.150).Cox multivariate analysis showed that MTDH expression was not an independent predictor of prognosis in patients with locally advanced triple negative breast cancer;3.Among 41 cases of locally advanced triple negative breast cancer,17 cases(41.5%)had high expression of AKT,and the expression of AKT was significantly correlated in DFS.DFS in patients with high expression of AKT was significantly shortened by 17.1 months(42.9 months vs.60 months,P = 0.041).There was no significant difference in OS between AKT high expression group and low expression group(52.8 Month vs.61.7 months,P = 0.112),and Cox multivariate analysis showed that AKT expression was not an independent predictor of prognosis in patients with locally advanced triple negative breast cancer;4.Among 41 cases of locally advanced triple negative breast cancer,12 cases had both high expression of MTDH and AKT before neoadjuvant chemotherapy.Both high expression and the number of lymph node metastasis after operation were significantly correlated with DFS and OS(DFS: P < 0.005;OS: P = 0.002).Cox multivariate analysis showed that both high expression of MTDH and AKT and the number of lymph node metastasis were independent predictors of DFS in patients with locally advanced triple negative breast cancer,and the number of lymph node metastasis after operation was an independent predictor of OS in those patients.Conclusions:1.High expression of MTDH and AKT is found in the patients of TNM stage III,Ki-67 > 30%,non bp CR,MP1-3 and histological grade 2-3,suggesting that the high expression of MTDH and AKT is related to the cancer development and treatment efficacy of triple negative breast cancer.2.High expression of MTDH and AKT is one of the factors that shorten DFS.Both high expression are an independent predictor of prognosis in patients with locally advanced triple negative breast cancer.