维甲酸受体β2和p16INK4α基因甲基化在食管鳞癌患者肿瘤组织和外周血中的表达  

DNA methylation status of RARβ2 and p16INK4α in peripheral blood and tumor tissue in patients with esophageal squamous cell carcinoma

作　　者：王长春[1] 毛伟敏[1] 凌志强[1] 

机构地区：[1]浙江省肿瘤医院浙江省肿瘤研究所肿瘤分子遗传实验室浙江省胸部肿瘤（食管、肺）诊治技术研究重点实验室,杭州310022

出　　处：《中华肿瘤杂志》2012年第6期441-445,共5页Chinese Journal of Oncology

基　　金：基金项目：浙江省科技计划（2009C33143）;浙江省自然基金（Y2080749、Y2091110）;人事部优秀留学回国人员科技活动项目（2008A004）;教育部优秀留学回国人员科研基金（2010609）

摘　　要：目的研究食管鳞癌患者肿瘤组织和外周血游离DNA中维甲酸受体β2（RARβ2）和p16INK4α基因的甲基化状态，以及围手术期血浆中RARe2和p16INK4α甲基化的动态变化，探讨血浆RARβ2和p16INK4α甲基化对食管鳞癌手术彻底程度的参考价值以及其与食管鳞癌患者临床病理特征的关系。方法采用实时甲基化特异性聚合酶链反应（real．timeMSP）技术，对76例食管鳞癌患者肿瘤组织、配对的癌旁正常组织、术前1d、术中（手术刚结束时）和术后第7天外周血游离DNA中RARβ2和p16INK4α基因的甲基化状态进行检测。随机选取60例年龄配对的健康志愿者外周血浆DNA作为对照。结果RARβ2和p16INK4α基因在食管鳞癌组织中的甲基化率分别为72．4％（55／76）和86．8％（66／76），在患者术前外周血中的甲基化率分别为63．2％（48／76）和71．1％（54／76），二者具有良好的一致性。外周血游离DNA中RARβ2和p16INK4α基因的甲基化与肿瘤病理分期、淋巴结转移以及神经脉管浸润均相关（均P〈0．05），外周血游离DNA中RARβ2基因的甲基化还与患者的肿瘤家族史相关（P=0．023），p16INK4α基因的甲基化还与肿瘤的浸润程度相关（P=0．037）。术前、术中、术后外周血游离DNA中RARβ2和p16INK4α基因的甲基化发生率均呈现先升后降的变化趋势。结论食管鳞癌患者外周血游离DNA中RARβ2和p16INK4α基因的甲基化可反映机体的荷瘤状态，并可作为判断食管鳞癌手术彻底程度的指标。Objective To study the methylation status of retinoic acid receptor 132 （RARe2） and p16INK4αgenes in peripheral blood and tumor tissues and the perioperative dynamic changes of free RARe2 and p16INK4α in the peripheral blood, and to investigate the relationship between RARe2 and p16INK4α methylation in peripheral blood and clinicopathological characteristics of esophageal squamous cell carcinoma （ESCC） and their value in evaluating the completeness of surgical resection. Methods Real-time methylation specific polymerase chain reaction （real-time MSP） technique was used to detect the methylation status of RARβ2 and p16INK4α in tumor tissue, adjacent normal tissue and peripheral blood periopemtively in 76 eases of ESCC. Sixty age-matched healthy volunteers were randomly selected as a control. Results RARβ2 and p16INK4αhypermethylation presented in both tumor tissue [72.4% （55/76） and 86.8% （66/76）] and peripheral blood [63.2% （48/76） and 71.1% （54/76） ] in the ESCC patients, showing a good agreement between them. RARβ2 and p16INK4αhypermethylation was significantly related with pathological stage, lymph node metastasis, and invasion of nerves and vessels （ P 〈 0.05 ）. The DNA methylation rate in peripheral blood was increasing first and then decreasing in the preoperative, intraoperative and postoperative periods. Moreover, the RARβ2 methylation in peripheral blood was shown to be significantly associated withfamily history of cancer （ P = 0. 023）. Conclusion RARβ and p16INK4α methylation in the peripheral blood in ESCC patients may reflect the tumor-bearing status in the body, and may serve as a valuable marker in assessment of the degree of completeness of surgical resection in ESCC patients.

关 键 词：食管肿瘤 DNA甲基化 外周血 手术期间 

分 类 号：R735.1[医药卫生—肿瘤]