Na-Yi Yuan Wu1, Xiaoyun Zhang1, Tangyuan Chu2, Songlin Zhu1, Yuping Deng1, Yi Zhou1, Ying Wang1, Xueheng Zhao1, Lu Liu1, Chao Fang3, Yang Wang4, Yu-Ligh Liou5, Jingting Cai1, Jing Wang1. 1. Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China. 2. Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Hulien, Taiwan, China. 3. The Third Xiangya Hospital, Central South University, Changsha 410000, China. 4. Hunan Hongya Gene Technology Co., Ltd., Changsha 410000, China. 5. Xiangya Medical Laboratory, Central South University, Changsha 410000, China.
Abstract
BACKGROUND: Our previous study demonstrated hypermethylation of the ZNF582 gene in cervical cancer, but its prognostic value in cervical cancer, especially in cervical adenocarcinoma (CAC), remains unclear. The present study aimed to investigate the value of ZNF582 gene methylation for diagnosis and prediction of radiochemotherapy sensitivity and prognosis in CAC. METHODS: We first determined ZNF582 methylation levels using quantitative methylation-specific PCR in a training set. Disease-free survival and overall survival (DFS and OS) rates were estimated using the Kaplan-Meier method. A Cox regression model was used to assess the prognostic significance of ZNF582 gene methylation in CAC patients. Immunohistochemistry was used to test ZNF582 protein expression in CAC tissues, and an MTT assay evaluated the sensitivity of Hela cells (with or without ZNF582 transfection) to radiation and chemotherapy. RESULTS: The ZNF582 gene showed a higher level of methylation in the CAC group than in the noncancer group, and patients negative for ZNF582 methylation had worse prognoses. We also found that ZNF582 methylation levels were reduced in concomitant chemo-radio-therapy (NCRT) patients compared with that in non-NCRT patients. Methylation-negative status was correlated with high ZNF582 protein expression, and ZNF582 protein overexpression could increase resistance to radiation and chemotherapy in Hela cells. CONCLUSIONS: Aberrant high methylation of ZNF582 may be a potential biomarker for CAC detection and prognosis monitoring. Overexpression of ZNF582 protein could increase CAC chemoradiotherapy resistance.
BACKGROUND: Our previous study demonstrated hypermethylation of the ZNF582 gene in cervical cancer, but its prognostic value in cervical cancer, especially in cervical adenocarcinoma (CAC), remains unclear. The present study aimed to investigate the value of ZNF582 gene methylation for diagnosis and prediction of radiochemotherapy sensitivity and prognosis in CAC. METHODS: We first determined ZNF582 methylation levels using quantitative methylation-specific PCR in a training set. Disease-free survival and overall survival (DFS and OS) rates were estimated using the Kaplan-Meier method. A Cox regression model was used to assess the prognostic significance of ZNF582 gene methylation in CAC patients. Immunohistochemistry was used to test ZNF582 protein expression in CAC tissues, and an MTT assay evaluated the sensitivity of Hela cells (with or without ZNF582 transfection) to radiation and chemotherapy. RESULTS: The ZNF582 gene showed a higher level of methylation in the CAC group than in the noncancer group, and patients negative for ZNF582 methylation had worse prognoses. We also found that ZNF582 methylation levels were reduced in concomitant chemo-radio-therapy (NCRT) patients compared with that in non-NCRT patients. Methylation-negative status was correlated with high ZNF582 protein expression, and ZNF582 protein overexpression could increase resistance to radiation and chemotherapy in Hela cells. CONCLUSIONS: Aberrant high methylation of ZNF582 may be a potential biomarker for CAC detection and prognosis monitoring. Overexpression of ZNF582 protein could increase CAC chemoradiotherapy resistance.
Authors: Hee J An; Kyu R Kim; In S Kim; Dong W Kim; Moon H Park; In A Park; Kwang S Suh; Eun J Seo; Sun H Sung; Jin H Sohn; Hye K Yoon; Eun D Chang; Hyun I Cho; Ji Y Han; Sung R Hong; Geung H Ahn Journal: Mod Pathol Date: 2005-04 Impact factor: 7.842
Authors: Hui-Juan Yang; Vincent W S Liu; Percy C K Tsang; Ann M W Yip; Tong-Yow Ng; Annie N Y Cheung; Hextan Y S Ngan Journal: Tumour Biol Date: 2003 Nov-Dec
Authors: Hung-Cheng Lai; Ya-Wen Lin; Tim H M Huang; Pearlly Yan; Rui-Lan Huang; Hui-Chen Wang; Joseph Liu; Michael W Y Chan; Tang-Yuan Chu; Chien-An Sun; Cheng-Chang Chang; Mu-Hsien Yu Journal: Int J Cancer Date: 2008-07-01 Impact factor: 7.396