scholarly journals Clinical Significance of Expression Changes and Promoter Methylation of PLA2R1 in Tissues of Breast Cancer Patients

2020 ◽  
Vol 21 (15) ◽  
pp. 5453
Author(s):  
Noha Mitwally ◽  
Einas Yousef ◽  
Ahmad Abd Al Aziz ◽  
Mohamed Taha

Phospholipase A2 receptor 1 (PLA2R1) expression and its role in the initiation and progression of breast cancer are an unresolved issue. PLA2R1 was found to endorse several tumor suppressive responses, including cellular senescence and apoptosis. Previous in vitro studies demonstrated that DNA hypermethylation was highly associated with the epigenetic silencing of PLA2R1 in breast cancer cell lines. Our objective was to study the level of PLA2R1 mRNA expression and the methylation of its promoter in different histological grades and molecular subtypes of breast cancer. We performed bioinformatics analyses on available human breast cancer expression datasets to assess the PLA2R1 mRNA expression. We used qRT-PCR to evaluate the PLA2R1 mRNA expression and its promoter’s methylation in breast cancer tissue in comparison to breast fibroadenomas. Our results describe, for the first time, the expression of PLA2R1 and the methylation of its promoter in human breast cancer tissues. A significant downregulation of PLA2R1, together with hypermethylation of the promoter was detected in breast cancers of different histological grades and molecular subtypes when compared to benign breast tissues. PLA2R1 promoter hypermethylation was associated with aggressive subtypes of breast cancer. In conclusion, PLA2R1 promoter hypermethylation is a potentially useful diagnostic and prognostic biomarker and could serve as a possible therapeutic target in breast cancer.

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 961 ◽  
Author(s):  
Srimeenakshi Srinivasan ◽  
Biana Godin

Over-expression of Crk-like protein (CrkL), an intracellular adaptor protein, in breast cancer biopsies has been linked to poor prognosis. CrkL can be secreted from cancer cells binding to β1 integrin on the cell membrane. In this study, we evaluated, for the first time, the levels of soluble CrkL in serum of breast cancer patients. Expression of CrkL and secreted fractions from human breast cancer cell lines and clinical patient samples were assessed by immunohistochemistry and Enzyme Linked Immuno-Sorbent Assay (ELISA). CrkL levels in tissues and sera of patients with different disease stages were compared and statistically analyzed by Chi-square test and Student’s t-test. Culture media from human breast cancer cell lines SUM159, MDA-MB231, and MCF7 showed over a 21-, 15-, and 11-fold higher concentration of soluble CrkL as compared to normal breast epithelium cell line MCF10A. Expression of CrkL was elevated in 85% of breast tumor tissue sections. Serum levels of CrkL were significantly higher in breast cancer patients than in healthy donors. All patients with metastatic disease had significantly elevated concentration of soluble CrkL in the serum with on average three-fold increase from the baseline. The data suggest that soluble fraction of CrkL can be further evaluated as a serum biomarker for advanced disease in breast cancer patients.


2009 ◽  
Vol 75 (9) ◽  
pp. 769-775 ◽  
Author(s):  
Sabina Siddiqui ◽  
C. Todd Bruker ◽  
Daniel P. Kestler ◽  
James S. Foster ◽  
Keith D. Gray ◽  
...  

Odontogenic Ameloblast Associated Protein (ODAM) is a protein isolated in ameloblasts during odontogenesis. ODAM expression was identified in breast cancer, but its significance remains unknown. The purpose of this study is to determine if ODAM expression can serve as a prognostic marker and provide information regarding treatment in human breast cancer. Breast cancer patients were identified from our tumor registry from 1993 to 2003. Archived breast cancer tissue from 243 patients (stage 0 = 53, stage I = 51, stage II = 53, stage III = 47, stage IV = 39) was stained using monoclonal antibody for ODAM. Presence or absence of immunostaining was correlated with stage, histologic grade, response to chemotherapy, and survival using χ2 and logistic regression analyses. Tumor nuclear staining for ODAM increased with increasing group stage ( P < 0.001). Staining for ODAM did not correlate with histologic grade or chemotherapy ( P = 0.558, P = 0.093). Improved outcomes within each stage were noted with ODAM staining, statistically significant for stages 0, I, and II ( P < 0.001, P = 0.003, P = 0.003) and underpowered for stages III and IV ( P = 0.724, P = 0.059). Survival benefit associated with tumor nuclear staining increased with advancing stage ( P < 0.001). These results show that ODAM predicts survival in breast cancer. Research is ongoing to determine ODAM's clinical utility and role in carcinogenesis.


2007 ◽  
Vol 246 (1-2) ◽  
pp. 253-261 ◽  
Author(s):  
Gilbert Spizzo ◽  
Guenther Gastl ◽  
Peter Obrist ◽  
Dominic Fong ◽  
Margot Haun ◽  
...  

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