| Objective: Breast cancer was one of the most common malignanttumors, which had higher incidence and mortality, and threatened the females’ life and health with a rising trend of incidence. Breast cancer was a systemic disease, and its therapeutic mode included operation, chemotherapy, endocrine therapy, radiotherapy and molecular targeted therapy etc.However, there was the phenomenon of multidrug resistance of breast cancer in clinic for tumor characteristics and individual heterogeneity of the patients. We predicted the problem of multidrug resistance of chemotherapy was a pressing problem in breast cancer therapy. With the study on the resistant molecular mechanism of breast cancer, the discovery of related biologic tumor markers has been the focus in medical research.Metaldherin, MTDH, was also called Astrocyte elevated gene-1(AEG-1). Some studies considered that high expression of MTDH gene in tumor cell could cause some results, including angiogenesis promoting, tumor cell proliferation, anti-apoptosis and decreased sensitivity of chemotherapeutic drugs to tumor cell etc. A lot of research confirmed that MTDH gene elevated tolerance function of tumor cell to various chemotherapeutic drugs by regulating downstream genes,such as hepatocyte growth factor receptor(c-Met) and tnf-related apoptosis-inducing ligand(TRAIL).MTDH gene knock-out caused the decreased expression of resistance gene and the increased expression of ALDH3A1, MET, HSP90 and promoting apoptosis gene(Bcl-2, BNIP3 and TRAIL). This study detected the expression of MTDH, c-Met and TRAIL in breast cancer tissue pre and post neo-adjuvant chemotherapy, and analyzed the association between the gene expression and biological characteristics of breast cancer for the discussion of the effect onMTDH, c-Met and TRAIL to chemotherapeutic efficacy.Methods:1 60 patients with stage II or stage III of primary breast cancer were selected, who hospitalized in Breast Center of the Fourth Hospital of Hebei Medical University should be treated with neo-adjuvant chemotherapy from July 2013 to December 2014. Tissue samples were selected by core needle biopsy before operation, and the patients were treated with surgery after administration of anthracycline and paclitaxel drug of 4 to 8 cycles. Tissue samples were selected on tumor bed during operation.The patients in the group were divided into sensitive group(c CR+c PR, n=44) and resistance group(SD+PD, n=16) according to RECIST 1.1 standard of entitative tumors. Postoperative tissue samples of residual tumor were evaluated and grouped according to Miller&Payne grading system, and there were a non-major histological reaction(NMHR) group with 35 cases from 1 grade to 3 grade and a major histological reaction group with 25 cases of 4 grade and 5 grade.2 The expression of MTDH, c-Met and TRAIL in 60 samples of breast cancer tissue pre and post chemotherapy was detected with one- step Max Vision TMimmunohistochemical method, and the relation among MTDH, c-Met, TRAIL pathological parameters of breast cancer was discussed. The grade of the immunohistochemistry results showed that- and + were low expression, and ++ and +++ were high expression. 3 60 tissue samples of breast cancer were analyzed to find out the association between the differential expression of MTDH, c-Met and TRAIL in sensitive group, resistance group, NMHR group and MHR group and sensitivity of chemotherapeutic drugs.4 The SPSS21.0 statistical software was used to analyse all of data. The chi-square test or Fisher definite probability methods were used to analyse the association between the expression of MTDH, c-Met and TRAIL and sundry clinicopathological parameters of breast cancer and chemotherapeutic efficacy. The results of each group were considered α=0.05 as significant level, and there was statistically significant difference with( P<0.05).Results:1 The expression of MTDH, c-Met and TRAIL in breast cancer tissue preand post neo-adjuvant chemotherapyThe high expression rates of MTDH,c-Met and TRAIL were 66.67%(40/60),55.0%(33/60) and 33.33%(20/60) before neo-adjuvant chemotherapyof breast cancer respectively,and the high expression rates of MTDH, c-Metand TRAIL were 50.0%(30/60), 38.33%(23/60) and 41.67%(25/60) afterneo-adjuvant chemotherapy respectively. There was no significant differenceof high expression pre and post chemotherapy(P>0.05).2 The association between the expression of MTDH,c-Met and TRAILand clinicobiological features of breast cancerThere were no statically significant differences of high expression ofMTDH and c-Met in breast cancer tissue in different age group, tumor sizegroup, ER group, PR group, Ki-67 group, HER2 and P53 group(P<0.05), butthere is significant difference of high expression of MTDH and c-Met betweenclinical stage group and axillary lymph node metastases group(P<0.05).There were no statically significant differences of the expression of TRAIL indifferent age group, tumor size group, ER group, PR group, Ki-67 group,HER2, P53 group, clinical stage group and axillary lymph node metastasesgroup(P<0.05).3 The association between the expression of MTDH, c-Met and TRAILand chemotherapeutic efficacyThe high expression rate of MTDH in sensitive group and resistancegroup were 56.8%(25/44)and 93.85%(15/16),respectively.The high expressionrate of c-Met in sensitive group and resistance group were 45.5%(20/44) and81.3%(13/16), respectively.The high expression rate of TRAIL in sensitivegroup and resistance group were 40.9%(18/44) and 12.5%(2/16), respectively.The differences was statically significant(P<0.05). The high expression rateof MTDH in NMHR group and MHR group were 82.9%(29/35) and 44.0%(11/25), respectively. The high expression rate of c-Met in NMHR group and MHR group were 71.4%(25/35) and 32%(8/25), respectively. The high expression rate of TRAIL in NMHR group and MHR group were 20%(7/35) and 52.0%(13/25), respectively. The differences was statically significant(P<0.05).Conclusions:1 MTDH and c-Met in breast cancer tissue were associated with TNM stage and lymph node metastasis. It indicated that MTDH and c-Met could involve in invasion and metastasis of breast cancer. TRAIL was unrelated to biological indexes of breast cancer.2 The high expression of MTDH and c-Met and the low expression of TRAIL in breast cancer tissue were associated with chemosensitivity of breast cancer. It indicated that MTDH, c-Met and TRAIL could predict chemotherapeutic efficacy and provide a new target for tumor therapy. |
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