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The Expression of COL11A1 and MMP3 are Dynamically Changed during the Carcinogenesis and Development of Breast Cancer and Might be Candidate Diagnostic and Prognostic Markers

Author: WangYuLi
Tutor: FengYuMei
School: Tianjin Medical University
Course: Biochemistry and Molecular Biology
Keywords: Breast Cancer COL11A1 MMP3 mRNA expression Occur Developing
CLC: R737.9
Type: Master's thesis
Year: 2007
Downloads: 45
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Abstract

Background: Breast cancer is one of the common female malignancy, although the diagnosis has improved continuously, and treatment measures continue to improve, but the mortality rate of the patients are still not effectively controlled. The onset and progression of breast cancer is involved in a variety of cancer-promoting gene activation and tumor suppressor gene inactivation of the co-ordination of the multi-step process of cumulative change, therefore, screening and breast cancer development related genes is to elucidate the mechanisms of breast cancer development, looking new diagnostic, the key prognostic molecular markers and therapeutic targets. Our group early in the next comparison of primary breast cancer, cancer and lymph node metastasis tissue gene expression profiles found: COL11A1 and MMP3 expression in primary breast cancer compared with paired cancer and adjacent normal breast tissue increases in lymph node metastatic tissues expression of primary compared to its paired breast cancer, down, suggesting that the amount of dynamic change of COL11A1 and MMP3 expression may play an important role in breast cancer incidence and development process, potential breast cancer diagnosis and metastasis prediction molecular markers. Objective: verified by clinical cases of the large sample size early gene chip results clarify the dynamic changes of the COL11A1 and MMP3 expression levels in breast cancer development and its relationship with clinicopathological factors, and to explore as a breast cancer diagnosis and prognosis of molecular the value of the markers. Method: using real-time quantitative RT-PCR was used to detect 30 cases of adjacent normal breast tissue, 30 cases of benign breast tumor, 107 cases of primary breast cancer and 30 cases of lymph node metastases COL11A1 and MMP3 the, mRNA expression levels, and analyze them in the breast cancer, and trends in the progress and its correlation with clinicopathological factors; mRNA in situ hybridization of the COL11A1 mRNA source histological positioning; using the Western blot method to detect breast cancer cell lines, in adjacent normal breast tissue, primary breast cancer and lymph node metastasis in cancer tissue COL11A1 protein and MMP3 protein expression levels and correlation analysis of protein expression and mRNA expression. Results: 1.COL11A1 gene expression in breast cancer development, the amount of dynamic change and its clinical significance. (1) COL11A1 mRNA expression in primary breast cancer is higher than the adjacent normal paired cancer (t = 4.442, P = 0.000); COL11A1 mRNA expression in metastases less than the primary breast cancer (t = 3.050, P = 0.005). (2) COL11A1 mRNA expression in benign breast tumor 2.70 times higher than in adjacent normal breast tissue (t = 2.622, P = 0.012); primary breast cancer COL11A1 mRNA mean expression levels is 67.47 times higher than in adjacent normal breast tissue ( t = 7.056, P = 0.000), 25.00 times higher than the benign breast tumor tissue (t = 6.866, P = 0.000); lymph node metastases than primary cancer reduced by 88.9% (t = 6.253, P = 0.000). (3) clinical stage I - Phase III group COL11A1 mRNA expression below Ⅳ group (P = 0.004); LN (4-9) group than in LN (0-3) group (P = 0.046); PR () group than the PR (-) group (P = 0.048); COL11A1 mRNA expression and patient age, tumor size, histological grade, no correlation between the expression of Her-2 and estrogen receptor status. (4) 2.0E-03 as a threshold, COL11A1 mRNA expression is divided into high expression group and the low expression group, 96.67% (29/30) of the cancer and adjacent normal breast tissue and 83.33% (25/30) of benign tumors of low expression, 81.31% (87/107) of primary breast cancer as high expression. The COL11A1 mRNA level of sensitivity for the diagnosis of breast cancer was 81.31%, a specificity of 90%. (5) Kaplan-Meier survival analysis showed that COL11A1 low expression of breast cancer patients with three-year metastasis-free survival in patients with high expression (P = 0.047). (6) COL11A1 mRNA derived from breast cancer cells, the small part of the surrounding stromal cells derived from cancer cells; COL11A1 mRNA expression was higher than in primary breast cancer cells in the lymph node metastasis of cancer cells. (7) COL11A1 protein expression in primary cancer of the same cases higher than in adjacent normal breast tissue and lymph node metastases compared with primary carcinoma of downward trend consistent with its mRNA expression, showed dynamic changes. COL11A1 protein 7 breast cancer cell lines to express the amount of mRNA expression trends, unrelated transfer cell infiltration biological behavior. Dynamic 2.MMP3 expression levels of genes in breast cancer development and its clinical significance in all cases (100%) (1) downregulation (t = 5.855, P = 0.000) in the primary cancer metastases compared with paired. 53.33% (16/30) next to the cancer cases Zhongyuan cancer than paired normal breast the middle COL11A1mRNA upregulation of 23.33% (7/30) of cases downregulated expression of the same amount of 23.33% (7/30) of cases. Average MMP3 mRNA expression levels (2) benign breast tumor tissue than in adjacent normal 11.66 times (t = 1.321, P = 0.197); primary breast cancer average MMP3 mRNA expression amount is higher than in adjacent normal breast tissue 2.93 times (t = 3.684, P = 0.000), with no significant differences in benign breast tumor (t = 1.081, P = 0.288); lymph node metastasis in cancer MMP3 mRNA expression than the primary cancer is reduced by 88.34% (t = 7.027, P = 0.00). Although there is no clinical pathological factors (3) MMP3 mRNA expression levels and patient age, tumor size, clinical stage, histological type, histological grade, lymph node status, Her2 and hormone status, but primary breast cancer MMP3 mRNA With the progress of the tumor, the expression level of the overall upward trend. (4) Kaplan-Meier survival analysis showed that MMP-3 low expression of metastasis-free survival in breast cancer patients was significantly higher than in patients with high expression (P = 0.0391). (5) MMP3 protein expression in the same cases of lymph node metastases compared with paired primary cancer downregulated, and its mRNA expression consistent trend. (6) MMP3 mRNA expression levels tended to increase with the enhanced cell invasion and metastasis ability. Conclusion: COL11A1 and MMP3 expression showed dynamic changes in breast cancer incidence and progression, they express the amount of the increase is a sign of poor prognosis in breast cancer patients. COL11A1 mRNA level detection with potential clinical value in the diagnosis of breast cancer.

The Expression of COL11A1 and MMP3 are Dynamically Changed during the Carcinogenesis and Development of Breast Cancer and Might be Candidate Diagnostic and Prognostic Markers

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