Wang Chang-chun, Mao Wei-min, Ling Zhi-qiang
Department of Molecular Genetics of Tumors, Zhejiang Cancer Research Institute, Zhejiang Provincial Cancer Hospital, Key Laboratory of Diagnosis and Treatment Technology of Thoracic Tumors, Hangzhou 310022, China.
Zhonghua Zhong Liu Za Zhi. 2012 Jun;34(6):441-5. doi: 10. 3760/cma.j.issn.0253-3766.2012.06.009.
To study the methylation status of retinoic acid receptor β2 (RARβ2) and p16(INK4α) genes in peripheral blood and tumor tissues and the perioperative dynamic changes of free RARβ2 and p16(INK4α) in the peripheral blood, and to investigate the relationship between RARβ2 and p16(INK4α) methylation in peripheral blood and clinicopathological characteristics of esophageal squamous cell carcinoma (ESCC) and their value in evaluating the completeness of surgical resection.
Real-time methylation specific polymerase chain reaction (real-time MSP) technique was used to detect the methylation status of RARβ2 and p16(INK4α) in tumor tissue, adjacent normal tissue and peripheral blood perioperatively in 76 cases of ESCC. Sixty age-matched healthy volunteers were randomly selected as a control.
RARβ2 and p16(INK4α) hypermethylation 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 p16(INK4α) hypermethylation 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 with family history of cancer (P = 0.023).
RARβ2 and p16(INK4α) 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.
研究维甲酸受体β2（RARβ2）和p16（INK4α）基因在外周血及肿瘤组织中的甲基化状态，以及外周血中游离RARβ2和p16（INK4α）的围手术期动态变化，并探讨外周血中RARβ2和p16（INK4α）甲基化与食管鳞状细胞癌（ESCC）临床病理特征的关系及其在评估手术切除完整性中的价值。
采用实时甲基化特异性聚合酶链反应（实时MSP）技术检测76例ESCC患者肿瘤组织、癌旁正常组织及围手术期外周血中RARβ2和p16（INK4α）的甲基化状态。随机选取60例年龄匹配的健康志愿者作为对照。
ESCC患者肿瘤组织[72.4%（55/76）和86.8%（66/76）]及外周血[63.2%（48/76）和71.1%（54/76）]中均出现RARβ2和p16（INK4α）高甲基化，二者之间具有良好的一致性。RARβ2和p16（INK4α）高甲基化与病理分期、淋巴结转移及神经和血管侵犯显著相关（P<0.05）。外周血DNA甲基化率在术前、术中和术后呈先升高后降低的趋势。此外，外周血中RARβ2甲基化与癌症家族史显著相关（P = 0.023）。
ESCC患者外周血中RARβ2和p16（INK4α）甲基化可能反映体内肿瘤负荷状态，并可作为评估ESCC患者手术切除完整性程度的有价值标志物。
