RECK基因甲基化与喉鳞状细胞癌预后的关系

Correlation between RECK gene methylation and the prognosis of laryngeal squamous cell carcinoma

目的喉癌发病率具有较大的区域性差异,其病因尚不明确。通过检测原发性喉鳞状细胞癌组织和癌旁组织RECK基因的甲基化状态,分析RECK基因启动子区的甲基化与患者预后的关系。方法采用甲基化特异性PCR检测邢台市人民医院2006年7月至2007年12月70例经外科手术切除的喉鳞状细胞癌标本的RECK基因启动子区甲基化状态,比较不同病理参数的甲基化率的差异,对完成5年随访的64例患者分析其RECK基因启动子区甲基化与预后的关系。结果肿瘤组织低分化患者的RECK基因甲基化率(86.67%)远高于中、高等分化程度的患者(43.64%),差异有统计学意义(P<0.05),其他病理参数间RECK基因甲基化率差异无统计学意义(P>0.05);29对喉鳞状细胞癌-癌旁组织匹配的标本中,喉鳞状细胞癌组织RECK基因甲基化率(55.12%)高于正常组织(27.59%),差异有统计学意义(P=0.029);经Log-rank分析,RECK基因甲基化可明显缩短患者的无瘤生存期和总体生存期(P=0.024,P=0.017);有淋巴结转移、Ⅲ-Ⅳ级临床分期可明显缩短患者的无瘤生存期和总体生存期(P=0.029,P=0.024;P=0.033,P=0.032),肿瘤组织中等及高分化可明显缩短患者的无瘤生存期(P=0.049);总体生存期的独立危险因素为有无淋巴结转移、临床分期和RECK基因甲基化。结论 RECK基因启动子区甲基化是人喉鳞状细胞癌的早期事件,在癌旁正常组织中也可发生,并且与患者较差的预后关联。

Objective The incidence of laryngeal cancer has characteristic of regional differences,but the etiology is not clear.The aim of this study was to analyze the correlation between RECK gene promoter methylation and prognosis of laryngeal squamous cell carcinoma patients through detecting the RECK gene methylation status of primary laryngeal squamous cell carcinoma and adjacent tissues.Methods Methylation specific PCR assay was used to detect the RECK gene promoter methylation status of 70 laryngeal squamous cell carcinoma specimens in our hospital from July 2006 to Dcember 2007,and the differences of methylation status with different pathological parameters were compared.The correlation between RECK gene promoter methylation and prognosis of 64 patients completed five-year follow-up was analyzed.Results The RECK gene methylation rate（ 86.67%） of patients with poor differentiation in tumor cells was much higher than that of the patients with a moderate and better tumor cell differentiation（ 43.64%）（ P ＆lt;0.05）.In 29 pairs of laryngeal cancer-adjacent tissues specimens matches,the RECK gene methylation in laryngeal carcinoma（ 55.12%） was higher than normal tissues（ 27.59%）（ P =0.029）.RECK gene methylation significantly shortened the tumor free survival and overall survival analyzed by Log-rank（ P = 0.024,P =0.017）.Lymph node metastasis and clinical stage in class Ⅲ-Ⅳ significantly shortened the tumor free survival and overall survival（ P =0.029,P =0.024; P =0.033,P =0.032）.Moderate and better tumor cell differentiation significantly shortened the tumor free survival（ P =0.024,P =0.049）.Lymph node metastasis,clinical stage,and RECK gene methylation were independent risk factors of overall survival.Conclusion RECK gene promoter methylation in human laryngeal squamous cell carcinoma is an early event and may occur in the adjacent normal tissues,predicting a poor prognosis in patients.