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Published on: October 27, 2014
Concurrent Wnt pathway component expression in breast and colorectal cancer
Maria Michelli1, Alexandros Zougros1, Ilenia Chatziandreou1
1First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, Athens, Greece.
Abstract:
Wnt signaling pathway regulates important cell functions such as proliferation and migration and is frequently deregulated in colorectal and breast cancer. Thus, it constitutes an attractive therapeutic target with many drugs being investigated in clinical trials. Eighty-two breast and 102 colorectal carcinomas were analyzed for: relative mRNA expression levels of Wnt pathway components namely Wnt3 ligand, Frizzled 7 receptor and LEF1 transcriptional factor, their concurrent expression patterns and their correlation with clinicopathological features. Regarding breast carcinomas, increased relative mRNA expression levels of WNT3 were found in 54 % of cases whereas decreased relative mRNA expression levels were observed in FZD7 and LEF1 in 82 % and 43 % of cases, respectively. Expression levels of WNT3 were significantly correlated with tumour grade (p = 0.021) in breast cancer. As far as colorectal carcinomas are concerned, increased relative mRNA expression levels of WNT3, FZD7 and LEF1 were found in 60 %, 37 % and 48 % of cases respectively. A statistically significant correlation emerged between LEF1expression levels and pT-category (p = 0.027), suggesting a possible association with tumour aggressiveness in colorectal carcinomas. Statistically significant linear correlations were observed between the expression of WNT3/LEF1 (R = 0.233, p = 0.035) and FZD7/LEF1 (R = 0.359, p = 0.001) in breast carcinomas as well as in colorectal carcinomas (R = 0.536, p < 0.01 and R = 0.210, p = 0.034) respectively. Our results demonstrate a possible clinical significance of Wnt pathway gene expression levels in both tumour types. The distinct expression patterns and simultaneous expression of the investigated genes underscore the complexity of this pathway in breast and colorectal carcinogenesis and highlights the necessity of patient selection with regard to the effectiveness of Wnt pathway inhibitors.
Insights
Wnt pathway gene expression in breast and colorectal cancers shows distinct patterns. Understanding these Wnt signaling variations is crucial for effective patient selection for Wnt pathway inhibitor therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The Wnt signaling pathway is vital for cell functions and often dysregulated in breast and colorectal cancers.
- This pathway is a key therapeutic target, with numerous drugs in clinical trials.
Purpose of the Study:
- To analyze Wnt pathway component mRNA expression (Wnt3, Frizzled 7, LEF1) in breast and colorectal carcinomas.
- To investigate concurrent expression patterns and correlations with clinicopathological features.
Main Methods:
- Quantitative analysis of Wnt3, Frizzled 7 (FZD7), and LEF1 mRNA expression levels in 82 breast and 102 colorectal tumors.
- Correlation analysis between gene expression levels and clinicopathological parameters.
Main Results:
- Breast cancer: Increased WNT3 (54%), decreased FZD7 (82%), decreased LEF1 (43%). WNT3 correlated with tumor grade (p=0.021).
- Colorectal cancer: Increased WNT3 (60%), FZD7 (37%), LEF1 (48%). LEF1 correlated with pT-category (p=0.027).
- Significant WNT3/LEF1 and FZD7/LEF1 correlations found in both cancer types.
Conclusions:
- Wnt pathway gene expression has potential clinical significance in breast and colorectal cancers.
- Distinct expression patterns highlight pathway complexity in carcinogenesis.
- Patient selection is essential for Wnt pathway inhibitor efficacy.
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