Clinical Significance of Receptor-Interacting Protein 3 and Parkin, Essential Molecules for Necroptosis, in Breast Cancer

원규연; Sun Young Min; Jeong-Yoon Song; Sung-Jig Lim; Sang-Ah Han

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자료유형: 학술저널

저자정보: 원규연 (Department of Pathology Kyung Hee University Hospital at Gangdong Kyung Hee University School of M) Sun Young Min (Department of Surgery Kyung Hee University School of Medicine Seoul Korea) Jeong-Yoon Song (Department of Surgery Kyung Hee University Hospital at Gangdong Kyung Hee University School of Med) Sung-Jig Lim (Department of Pathology Kyung Hee University Hospital at Gangdong Kyung Hee University School of M) Sang-Ah Han (Department of Surgery Kyung Hee University Hospital at Gangdong Kyung Hee University School of Med)

저널정보: 한국유방암학회 Journal of Breast Cancer Journal of Breast Cancer Vol.24 No.1

발행연도: 2021.1

수록면: 34 - 48 (15page)

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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.

#Breast neoplasms #Necroptosis #Parkinson disease associated proteins #Receptor interacting protein serine-threonine kinase 3

참고문헌 (8)

참고문헌 신청

Buchheit CL / 2012 / The regulation of cancer cell death and metabolism by extracellular matrix attachment / Semin Cell Dev Biol 23:402~411

Fu Z / 2013 / The anti-tumor effect of shikonin on osteosarcoma by inducing RIP1 and RIP3 dependent necroptosis / BMC Cancer 13:580

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Shimura H / 2000 / Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase / Nat Genet 25:302~305

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원규연

소속기관 Department of Pathology Kyung Hee University Hospital at Gangdong Kyung Hee University School of M