Wiphawan Wasenang1, Anucha Puapairoj2, Chatri Settasatian2, Siriporn Proungvitaya3, Temduang Limpaiboon4. 1. Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand; Biomedical Sciences, Graduate School, Khon Kaen University, Khon Kaen, 40002, Thailand. 2. Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. 3. Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand; Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. 4. Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand; Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. Electronic address: temduang@kku.ac.th.
Abstract
BACKGROUND: Cholangiocarcinoma (CCA) is a fatal liver cancer arising from bile duct epithelium. Polycomb repressive complex 2 (PRC2) is a histone methyltransferase enzyme that catalyzes trimethylation of histone H3 on lysine 27, resulting transcriptional gene silencing. The key components of PRC2 are EZH2, SUZ12 and EED, which EZH2 is a catalytic subunit. The defect of individual PRC2 components has been shown to enhance carcinogenesis and cancer progression. The aim of this study was to determine the expression of individual PRC2 components and evaluate its association with clinicopathological data in CCA patients. METHODS: The expression of PRC2 components including EZH2, SUZ12 and EED was determined by immunohistochemistry in 40 CCA tissue samples. RESULTS: The expression of EZH2 and SUZ12 in CCA tissue was significantly higher than that in adjacent non-cancerous tissue (P < 0.001). The high cytoplasmic EZH2 expression was significantly associated with short overall survival in CCA (P = 0.030). Interestingly, a combined high nuclear and cytoplasmic expression of EZH2 was found to be a worse prognostic marker for overall survival (P = 0.015). Moreover, combined high expression of EZH2 and SUZ12/EED was also associated with short overall survival (P < 0.05). CONCLUSIONS: Our findings suggest that overexpression of the PRC2 key components especially EZH2 in both nucleus and cytoplasm can be potentially used as a prognostic marker for CCA.
BACKGROUND:Cholangiocarcinoma (CCA) is a fatal liver cancer arising from bile duct epithelium. Polycomb repressive complex 2 (PRC2) is a histone methyltransferase enzyme that catalyzes trimethylation of histone H3 on lysine 27, resulting transcriptional gene silencing. The key components of PRC2 are EZH2, SUZ12 and EED, which EZH2 is a catalytic subunit. The defect of individual PRC2 components has been shown to enhance carcinogenesis and cancer progression. The aim of this study was to determine the expression of individual PRC2 components and evaluate its association with clinicopathological data in CCA patients. METHODS: The expression of PRC2 components including EZH2, SUZ12 and EED was determined by immunohistochemistry in 40 CCA tissue samples. RESULTS: The expression of EZH2 and SUZ12 in CCA tissue was significantly higher than that in adjacent non-cancerous tissue (P < 0.001). The high cytoplasmic EZH2 expression was significantly associated with short overall survival in CCA (P = 0.030). Interestingly, a combined high nuclear and cytoplasmic expression of EZH2 was found to be a worse prognostic marker for overall survival (P = 0.015). Moreover, combined high expression of EZH2 and SUZ12/EED was also associated with short overall survival (P < 0.05). CONCLUSIONS: Our findings suggest that overexpression of the PRC2 key components especially EZH2 in both nucleus and cytoplasm can be potentially used as a prognostic marker for CCA.
Authors: Brajendra K Tripathi; Meghan F Anderman; Disha Bhargava; Luciarita Boccuzzi; Xiaolan Qian; Dunrui Wang; Marian E Durkin; Alex G Papageorge; Fernando J de Miguel; Katerina Politi; Kylie J Walters; James H Doroshow; Douglas R Lowy Journal: Nat Commun Date: 2021-12-03 Impact factor: 14.919