Expression Of Matrix Metalloproteinases-9 (MMP-9) And Glioma-associated Oncogene Homolog (GLI-1) Predicts The Relapse/metastasis In Breast Cancer

Background and Objective:Breast cancer is a significant world wild public health problem. Despite major advances in adjuvant therapy, improvement in survival has been disappointingly small.Targeting patients appropriately for adjuvant therapy is currently based on the tumor-node-metastasis(TNM) system and other clinicopathological prognostic factors. Recent interest has focused on developing laboratory methods to identify new factors that associated with poor progress of breast cancer patients.The degradation of extracellular matrix surrounding both the primary tumor and tumors at distant sites is a critical step in invasion and metastasis of breast cancer. The degradative process mainly is catalyzed by the matrix metalloproteinasess (MMPs).The Hedgehog signaling pathway is known to be essential for multiple aspects of embryonic development. The transcription factor GLI-1, a member of the GLI subfamily is involved in signal transduction within the Hedgehog pathway. Aberrant Hedgehog signaling has been implicated in the development of different humor tumor entities including tumors of skin, pancreas, prostate and breast cancer. Further, the malignancy of tumors and their progression to metastatic stages have been associated with activity of the Hedgehog signaling pathway.Recent studies suggest that the malignancy of tumors and their progression to metastasis stages have been associated with activity of the Hedgehog signaling pathway. And an association was found between the expression of GLI-1 and depth of tumor invasion, status of lymph node metastasis, as well. But studies of the correlation between the GLI-1 and the clinicopathological characteristics have not draw a unified conclusion.Method:We chose the breast cancer patients that were confirmed by pathological examination in our hospital between 2001-1-1-2004-12-31. We collected the clinicopathological characteristics and the outcomes of these patients, there are 42 patients suffering from cancer relapse, and these 42 patients formed the "Recurrence-Team", and then we picked up another 42 from the rest of the patients randomly, these patients formed the "Healthy-Team". Meanwhile, we chose up ten benign breast tumor patients as the "negative-control" team.And then, we performed a systematic expression analysis of MMP-9 and GLI-1 in human breast cancer on the protein level and correlated the MMP-9 and GLI-1 expression levels with other clinicopathological characteristics.Result:1. Overexpression of the MMP-9 and GLI-1 are associated with poor progress of breast cancer patients.2. Positive-expression of MMP-9 significantly associated with patient's age, pT and metastasis to bone.3. Overexpression of GLI-1 is associated with unfavorable overall survival of breast cancer patients. A significant correlation was found between increased expression of GLI-1 and patient age, lymph node status, oestrogen receptor and liver/bone metastasis of the analysed tumors.Conclusions:The result based on our experiment supporting a role of MMP-9 and GLI-1 as new prognostic marker of breast cancer.