Polo-like kinase 4 as a potential predictive biomarker of chemoradioresistance in locally advanced rectal cancer
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase located in the centriole of the chromosome during the cell cycle. PLK4 overexpression has been described in a variety of many common human epithelial tumors. Conversely, PLK4 acts as a haploinsufficient tumor suppressor in some situations, highlighting the importance of strict regulation of PLK4 expression, activity, and function. Meanwhile, the importance of chemoradiation resistance in rectal cancer is being emphasized more than ever. We aimed to analyze PLK4 expression and the tumor regression grade (TRG) in patients with rectal cancer, treated with chemoradiotherapy (CRT).Methods: A retrospective study was conducted on 102 patients with rectal cancer who received preoperative CRT. Immunohistochemistry for PLK4 in paraffin-embedded tissue was performed from the biopsy and surgical specimens. Results: We found significant association between high expression of PLK4 and poor response to neoadjuvant CRT (according to both Mandard and The Korean Society of Pathologists TRG systems) in the pre-CRT specimens. Other clinicopathologic parameters did not reveal any correlation with PLK4 expression. Conclusions: This study revealed an association between high expression of PLK4 in the pre-CRT specimens and TRG. Our results indicated that PLK4 could potentially be a new predictor for CRT effect in patients with rectal cancer.
Abstract
Background: Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase located in the centriole of the chromosome during the cell cycle. PLK4 overexpression has been described in a variety of many common human epithelial tumors. Conversely, PLK4 acts as a haploinsufficient tumor suppressor in some situations, highlighting the importance of strict regulation of PLK4 expression, activity, and function. Meanwhile, the importance of chemoradiation resistance in rectal cancer is being emphasized more than ever. We aimed to analyze PLK4 expression and the tumor regression grade (TRG) in patients with rectal cancer, treated with chemoradiotherapy (CRT).Methods: A retrospective study was conducted on 102 patients with rectal cancer who received preoperative CRT. Immunohistochemistry for PLK4 in paraffin-embedded tissue was performed from the biopsy and surgical specimens. Results: We found significant association between high expression of PLK4 and poor response to neoadjuvant CRT (according to both Mandard and The Korean Society of Pathologists TRG systems) in the pre-CRT specimens. Other clinicopathologic parameters did not reveal any correlation with PLK4 expression. Conclusions: This study revealed an association between high expression of PLK4 in the pre-CRT specimens and TRG. Our results indicated that PLK4 could potentially be a new predictor for CRT effect in patients with rectal cancer.
참고문헌 (18)
- Camma C, "Preoperative radiotherapy for resectable rectal cancer : a meta-analysis", JAMA, 284, pp.1008~1015 (2000)
- Bettencourt-Dias M, "SAK", PLK4 is required for centriole duplication and flagella development, 2005, pp.15, 2199~2207
- Habedanck R, "The Polo kinase Plk4 functions in centriole duplication", Nat Cell Biol, 7, pp.1140~1146 (2005)
- Sillibourne JE, "Autophosphorylation of polo-like kinase 4 and its role in centriole duplication", Mol Biol Cell, 21, pp.547~561 (2010)
- Rodrigues-Martins A, "Revisiting the role of the mother centriole in centriole biogenesis", Science, 316, pp.1046~1050 (2007)
- Macmillan JC, "Comparative expression of the mitotic regulators SAK and PLK in colorectal cancer", Ann Surg Oncol, 8, pp.729~740 (2001)
- Mason JM, "Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent", Cancer Cell, 26, pp.163~176 (2014)
- Denu RA, "Centrosome amplification induces high grade features and is prognostic of worse outcomes in breast cancer", BMC Cancer, 16, pp.47~ (2016)
- Coelho PA, "Over-expression of Plk4induces centrosome amplification, loss of primary cilia and associated tissue hyperplasia in the mouse", Open Biol, 5, pp.150209~ (2015)
- Sercin O, "Transient PLK4 overexpression accelerates tumorigenesis in p53-deficient epidermis", Nat Cell Biol, 18, pp.100~110 (2016)
- Ko MA, "Plk4 haploinsufficiency causes mitotic infidelity and carcinogenesis", Nat Genet, 37, pp.883~888 (2005)
- Rosario CO, "Plk4 is required for cytokinesis and maintenance of chromosomal stability", Proc Natl Acad Sci U S A, 107, pp.6888~6893 (2010)
- Kazazian K, "Plk4 promotes cancer invasion and metastasis through Arp2", 3 complex regulation of the actin cytoskeleton, 2017, pp.77, 434~447
- Mandard AM, "Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma : clinicopathologic correlations", Cancer, 73, pp.2680~2686 (1994)
- 김백희, "Standardized Pathology Report for Colorectal Cancer, 2nd Edition", Journal of Pathology and Translational Medicine, 54(1), pp.1~19 (2020), 대한병리학회[DOI]
- McCarty KS Jr, "Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies", Arch Pathol Lab Med, 109, pp.716~721 (1985)
- Wang J, "Pololike kinase 4 promotes tumorigenesis and induces resistance to radiotherapy in glioblastoma", Oncol Rep, 41, pp.2159~2167 (2019)
- Li Z, "Expression of polo-like kinase 4(PLK4)in breast cancer and its response to taxane-based neoadjuvant chemotherapy", J Cancer, 7, pp.1125~1132 (2016)