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1、Analysis Of The Correlation Of MiR-498、miR-let-7d And MiR-let-7e With The Breast Cancer 2、Clinical And Prognostic Analysis Of Phyllodes Tumors Of The Breast

Posted on:2016-06-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:H WangFull Text:PDF
GTID:1224330461976660Subject:Oncology
Abstract/Summary:PDF Full Text Request
Objective The aim of this study is to explore the differences in clinical and pathological characteristics between benign, borderline and malignant phyllodes tumors, and to investigate the predictive factors that affecting the disease-free survival of this tumor as well.Methods Data from 246 women with Phyllodes Tumors of the breast treated in Cancer Hospital Chinese Academy of Medical Sciences between January 2002 and December 2012 was collected and analyzed retrospectively, including age at presentation and treatment, course, intial size of tumor, location, histological type, ulceration, type of primary surgery and date, local recurrence, distant metastasis, fibroadenoma history, pathological changes during recurrence, times of recurrence and treatment after surgery, with a follow-up to May 20th,2014. The median follow-up was 48 months.56 patients had local recurrence,5 patients had distant metastasis, while 1 person had both local recurrence and distant metastasis.65 droped out.Results In univariate analysis between three histological types, average age at presentation, average age at treatment, size of primary tumor, ulceration or not, type of primary surgery and distant metastasis turned out to be statistically different among the three PT groups (p=0.014,0.018,<0.000,0.003,<0.000,0.001, respectively), while recurrence and disease-free survival (DFS) demonstrated trends for statistical significance (P=0.055 and 0.060, respectively). Multivariate analysis revealed distant metastasis and excision were significantly different in benign, borderline and malignant phyllodes tumors of the breast (p=0.041 and 0.018, OR=0.061 and 0.051). At the same time, size of primary tumor with p=0.052 tended to be different between groups (OR=1.127). Kaplan-Meier survival analysis displayed that fibroadenoma history could predict recurrence with p<0.000 and local excision had higher risk of recurrence than total mastectomy and modified radical mastectomy with p=0.043, while the risk tended to malignant>borderline>benign with a p value 0.083. In the Cox Proportional Hazard Model multianalysis, type of primary surgery, fibroadenoma history and histological types were all statistically significant(P=0.009,0.001 and 0.000).Conclusions Benign borderline and malignant phyllode tumors have different distant metastasis risk, different primary tumor size and different surgical procedures, and malignant PTs are more likely to be bigger and to metastasize. Besides, type of primary surgery, fibroadenoma history and histological types are independent factors predicting the disease-free survival of phyl lodes tumors.Objective:We aimed to find out the expression of miR-498, miR-let-7d5p, miR-let-7d3p, miR-let-7e5p and miR-let-7e3p in breast cancer tissue, as well as the relationship of miR-498, miR-let-7d5p, miR-let-7d3p, miR-let-7e5p and miR-let-7e3p with the clinical and pathological characteristics of breast cancer patients.Methods:In our previous study, microarray analysis has been used to find out miRNAs that are involved in EMT, comparing MCF-10A cells before and after Snail-induced EMT. The expression levels of miR-498 is found to be upregulated after EMT in mammary epithelial model systems, which imply that maybe this miRNA could inhibit the process of EMT. Besides, we used a microRNA virus library pool, containing about a thousand kinds of microRNAs precusors. We infected non-migratory breast cancer cells MCF-7 with this pool, and then, we used a transwell invasion assay to select the cells. The cells migrated through the membrane were collected, enriched, and formed monoclones. Finally, we sequenced the genomic DNA of these monoclones to identify the microRNAs, which may promote cell invasion. miR-let-7d and miR-let-7e were found. Then qRT-PCR was used to quantify the expression of miR-498, miR-let-7d5p, miR-let-7d3p, miR-let-7e5p and miR-let-7e3p in breast normal and cancer tissue. Meanwhile, the clinical and pathological characteristics of breast cancer patients were collected.Results:Compared with breast normal tissues, the expression of miR-498, miR-let-7d3p and miR-let-7e3p was downregulated in breast cancer tissues with P=0.0004,0.0012 and 0.0453. The expression of miR-let-7d3p was related with menarche age, P53 and lymphovascular involvement(P=0.0177,0.0044 and 0.0166).The findings also suggested miR-let-7e5p was strongly associated with ER, PR, EGFR and Oncotype(P=0.0091, 0.0096,0.0166 and 0.0287), had nothing to do with Her-2 and Ki-67(P=0.6733, P=0.8121), and demonstrated a statistically significant trend with CK5&6(P=0.0550). miR-let-7e3p was inversely correlated with lymphovascular involvement(P=0.0398).Conclusions:miR-498, miR-let-7d3p and miR-let-7e3p may inhibit the tumorigenesis in breast cancer. The expression of miR-let-7d3p was upregulated in patients with late menarche and absent lymphovascular involvement, which suggests miR-let-7d3p may perform as a protective factor, however the relationship with P53 remains unkown. The upregulation of miR-let-7e5p in patients of ER(+), PR(+),CK5&6(-). EGFR(-) and Luminal type indicates miR-let-7e5p may be a favorable factor, though the exct mutual mechanism is unclear. The relationship of miR-let-7e3p with lymphovascular involvement may imply miR-let-7e3p could inhibit metastasis of breast cancer.
Keywords/Search Tags:Breast cancer, EMT(epithelial mesenchymal transition), miR-498, miR-let-7d5p, miR-let-7d3p, miR-let-7e5p, miR-let-7e3p, Phyllodes tumors of the breast, Benign, Borderline, Malignant, Recurrence, Disease-free survival
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