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Methylation of IRAK3 is a novel prognostic marker in hepatocellular carcinoma

World Journal of Gastroenterology 2015年第13期21卷 3960-3969页

作者： Chih-Chi Kuo Yu-Lueng Shih Her-Young Su Ming-De Yan Chung-Bao Hsieh Chin-Yu Liu Wei-Ting Huang Mu-Hsien Yu Ya-Wen Lin Graduate Institute of Medical Sciences National Defense Medical Center Division of Gastroenterology Department of Internal MedicineTri-Service General HospitalNational Defense Medical Center Department of Obstetrics and Gynecology Tri-Service General HospitalNational Defense Medical Center Cancer Center Wan Fang HospitalTaipei Medical University Division of General Surgery Department of SurgeryTri-Service General HospitalNational Defense Medical Center Department of Nutritional Science Fu Jen Catholic University Department and Graduate Institute of Microbiology and Immunology Graduate Institute of Medical SciencesNational Defense Medical Center Graduate Institute of Life Sciences National Defense Medical Center

AIM: To examine the methylation levels of interleukin-1 receptor-associated kinase 3(IRAK3) and gloxd1 and their potential clinical applications in hepatocellular carcinoma(HCC).METHODS: m RNA expression and promoter methylation of IRAK3 and gloxd1 in HCC cells were analyzed by reverse transcription-polymerase chain reaction(RTPCR) and methylation-specific PCR(MSP), respectively. Using pyrosequencing results, we further established a quantitative MSP(Q-MSP) system for the evaluation of IRAK3 and gloxd1 methylation in 29 normal controls and 160 paired HCC tissues and their adjacent nontumor tissues. We also calculated Kaplan-Meier survival curves to determine the applications of gene methylation in the prognosis of ***: IRAK3 and gloxd1 expression was partially restored in several HCC cell lines after treatment with 5-aza-2′-deoxycytidine(DNA methyltransferase inhibitor; 5DAC). A partial decrease in the methylated band was also observed in the HCC cell lines after 5DAC treatment. Using gloxd1 as an example, we found a significant correlation between the data obtained from the methylation array and from pyrosequencing. The methylation frequency of IRAK3 and gloxd1 in HCC tissues was 46.9% and 63.8%, respectively. Methylation of IRAK3 was statistically associated with tumor stage. Moreover, HCC patients with IRAK3 methylation had a trend toward poor 3-year disease-free survival(P gloxd1 were frequently methylated in HCC tissues compared to normal controls and nontumor tissues. IRAK3 methylation was associated with tumor stage and poor prognosis of patients. These data suggest that IRAK3 methylation is a novel prognostic marker in HCC.

关键词： IRAK3 gloxd1 Hepatocellular carcinoma DNA methylat

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