The Study On Expression Of MTDH Gene In Breast Cancer And Its Correlation With Neo-adjuvant Chemotherapy

Objective: MTDH(metadherin), also known as Astrocyte elevatedgene-1(AEG-1), is a proto-oncogene discovered recently. It showed highexpression in tumor tissues of the different organs in human body, includingmelanoma, hepatocellular carcinoma, lung cancer, and breast cancer. MTDHgene could regulate the growth and proliferation of tumor cell, and furtheraffect its progress and metastasis. While there are few studies focus on thefunction of MTDH in pathological and physiological course of breast cancer.And the literatures were rare that revealed the relationship between MTDHand neo-adjuvant chemotherapy in breast cancer. In this study we detectedMTDH expression in normal breast tissue and in breast cancer tissue (beforeand after neo-adjuvant chemotherapy) and analyzed the correlation betweenMTDH expression and the biological characteristics of breast cancer, and alsodiscussed the relationship of MTDH with progress and metastasis andchemosensitivity of breast cancer so as to find a molecular biologic marker forpredicting the prognosis and chemosensitivity.Method: In the study44cases with breast cancer were selected, whowere proved to be breast invasive ductal carcinoma by pathological diagnosisin Breast Center of Fourth Hospital of Hebei Medical University, from March2010to December2011. All patients were treated with anthracycline drug andpaclitaxel drug for neo-adjuvant chemotherapy. We detected the samples fromcarcinoma of44patients before and after neo-adjuvant chemotherapy and10patients with benign breast disease. Flow cytometry was used to detect MTDHexpression in all of above tissues. And the relationships were analyzed, suchas MTDH and effect of chemotherapy, MTDH and tumor size, TNM stage,lymph node metastasis, histological grade, or the expression of ER, PR andHER-2. Results:1Expression of MTDH in breast cancer tissue before and afterneo-adjuvant chemotherapy and normal breast tissueThe MTDH expression was10.30±3.56before neo-adjuvantchemotherapy, and was8.74±3.42after neo-adjuvant chemotherapy. MTDHexpression of normal breast tissue is5.32±2.04. The level of MTDHexpression before neo-adjuvant chemotherapy was obviously higher than thatof after neo-adjuvant chemotherapy,(P＜0.05). And the level of MTDHexpression in breast cancer tissues (incloding before and after neo-adjuvantchemotherapy) was higher than that of in normal breast tissue,(P<0.05).2Relationship between the expression of MTDH and the biologicalcharacteristics of breast cancerIn the group of44patients, the MTDH expression gradually increasedwith the growth of tumor size(F=3.851, P=0.03), histological grade (F=5.291,P=0.009) and lymph node metastasis (F=19.483, P=0.000). There was nosignificant correlation between MTDH protein expression and menstrualstatus (t=1.57, P=0.122), ER (t=0.272, P=0.788), PR (t=-0.427, P=0.671) andHER-2(t=0.528, P=0.621).3Relationship between the expression of MTDH before neo-adjuvantchemotherapy and the effect of chemotherapyWe statistically analysised the relationship between MTDH expressionlevel and neo-adjuvant chemotherapy clinical effect, which found that CR andPD (t=-2.658, P=0.029), PR and SD (t=-2.364,P=0.024), PR and PD(t=-3.153, P=0.004).Each combination of two groups had no statisticalsignificance, CR and PR (t=0.065,P=0.949), CR and SD (t=-1.814,P=0.091),SD and PD (t=-2.092,P=0.063). The expressions of MTDH are9.38±3.29inCR+PR group and13.03±2.73in SD+PD group. There was significantdifference between CR+PR group and SD+PD group,(t=-3.55,P＜0.05).Conclusion:1MTDH expression in breast cancer tissue is significantly higher thanthat in normal breast tissue and there is a positive correlation between MTDH and TNM staging, lymph node metastasis and histological grade, whichindicate that it may be possible close relation to MTDH and breast canceroccurrence and progression.2The effective rate of neo-adjuvant chemotherapy is obviously low inthe patients with high MTDH expression, while is high in the patients withlow MTDH expression which suggests that it is possible that MTDH may be aeffective marker for predicting the effect of chemotherapy in breast cancer.