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Published on: May 4, 2016
Clinical Significance of Receptor-Interacting Protein 3 and Parkin, Essential Molecules for Necroptosis, in Breast
Kyu Yeoun Won1, Sun Young Min2, Jeong Yoon Song3
1Department of Pathology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.
Purpose:
Receptor-interacting protein 3 (RIP3) is the main initiator of necroptosis. Parkin prevents the formation of the RIP1-RIP3 complex by promoting polyubiquitination of RIP3. However, the mechanism by which necroptosis affects the clinical features of breast cancer and prognosis is not known. Here, we aimed to study the effect of necroptosis on the clinical features and prognosis of breast cancer by assessing the expression of RIP3 and Parkin.
Methods:
Tissue microarrays (TMAs) were constructed from 257 cases of breast cancer. Immunohistochemistry was performed on 4-μm tissue sections from each TMA block. The χ² test, Kaplan-Meier survival analysis with log-rank test, and Cox regression proportional hazard model were used for statistical analysis.
Results:
Low RIP3 expression resulted in a large tumor size and high nuclear grade. Low RIP3 expression was correlated with human epidermal growth factor receptor 2 positivity, short overall survival (OS), and short disease-free survival (DFS). The triple negative breast cancer group with low RIP3 expression and lymph node (LN) positive group with low RIP3 expression had the shortest OS. High Parkin expression was associated with high histological grade, estrogen and/or progesterone receptor negativity, and lymphatic emboli, but was not correlated with OS and DFS. OS was correlated with LN metastasis and RIP3 loss and DFS with large tumor size, LN metastasis, and RIP3 loss.
Conclusion:
Low RIP3 and high Parkin expression are associated with aggressive clinical features in breast cancer. RIP3, a molecular marker of necroptosis, is an independent factor associated with survival in breast cancer. Further in-depth studies are needed to investigate the role of necroptosis in breast cancer development, metastasis, and treatment in the future.
Insights
Receptor-interacting protein 3 (RIP3) loss and high Parkin expression indicate aggressive breast cancer. RIP3 is a key marker for necroptosis and predicts patient survival, suggesting its role in breast cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Pathways
Background:
- Receptor-interacting protein 3 (RIP3) initiates necroptosis, a programmed cell death pathway.
- Parkin regulates RIP3 ubiquitination, potentially inhibiting necroptosis.
- The role of necroptosis in breast cancer clinical features and prognosis remains unclear.
Purpose of the Study:
- To investigate the impact of necroptosis, specifically RIP3 and Parkin expression, on breast cancer clinical characteristics and patient outcomes.
- To assess RIP3 and Parkin as potential prognostic markers in breast cancer.
Main Methods:
- Tissue microarrays from 257 breast cancer cases were analyzed using immunohistochemistry.
- Statistical analyses included the χ² test, Kaplan-Meier survival analysis, and Cox regression models.
Main Results:
- Low RIP3 expression correlated with larger tumor size, higher nuclear grade, HER2 positivity, and shorter overall survival (OS) and disease-free survival (DFS).
- Triple-negative and lymph node-positive breast cancers with low RIP3 expression showed the shortest OS.
- High Parkin expression was linked to adverse features like high histological grade and lymphatic emboli but not OS or DFS.
Conclusions:
- Reduced RIP3 and elevated Parkin expression are associated with aggressive breast cancer phenotypes.
- RIP3 expression serves as an independent prognostic factor for survival in breast cancer patients.
- Further research is warranted to elucidate the role of necroptosis in breast cancer development, metastasis, and therapeutic strategies.
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