RASSF1A基因启动子区甲基化在贲门腺癌、食管下段鳞癌组织中的变化及临床意义

Clinical significance of RASSF1A promoter methylation in gastric cardiac carcinoma and esophageal squamous cell carcinoma

目的:比较RASSF1A基因甲基化在贲门腺癌、食管下段鳞癌不同病理阶段组织中的共性和差异.方法:33例贲门腺癌和36例食管下段鳞癌手术切除标本纳入本研究,每例标本选取癌组织,癌旁不典型增生组织(距癌3-5cm),癌旁正常组织(距癌>5cm)组织各1块,采用甲基化特异性PCR检测RASSF1A基因启动子区的甲基化情况.结果:贲门腺癌癌组织、癌旁不典型增生组织和癌旁正常组织中RASSF1A基因启动子区甲基化的发生率分别为63.6%,20%,4.2%;食管下段鳞癌癌组织、癌旁不典型增生组织和癌旁正常组织中RASSF1A基因启动子区甲基化的发生率分别为66.7%,25%,16.7%.随着病变程度的加重(癌旁正常组织-癌旁不典型增生组织-癌组织),贲门腺癌患者RASSF1A基因启动子区甲基化的发生率呈上升趋势(χ2=22.173,P<0.001),食管下段鳞癌患者RASS-F1A基因启动子区甲基化的发生率亦呈上升趋势(χ2=19.324,P<0.001),但两者的升高幅度不同.贲门腺癌癌旁正常组织中RASSF1A基因启动子区甲基化的发生率明显低于食管下段鳞癌癌旁正常组织.结论:RASSF1A基因启动子区高甲基化是贲门腺癌和食管下段鳞癌发生的共同分子事件,RASSF1A基因可作为胃食管交界部癌患者早期诊治和监测的候选指标.

AIM： To investigate the methylation status of the promoter region of the RASSF1A gene in gastric cardiac adenocarcinoma （GCA） and esophageal squamous cell carcinoma （ESCC） in the distal esophagus and to analyze their clinical significance. METHODS： Thirty-three GCA patients and 36 ESCC patients who came from a high-incidence region of ESCC in Linzhou, Henan and were treated at Yaocun Esophageal Cancer Hospital and Linzhou Center Hospital were enrolled inthis study. No statistical differences were found in sex, age, and tumor differentiation between GCA and ESCC patients. No patients received chemotherapy or radiotherapy before operation. Methylation-specific polymerase chain reaction （MSP） was used to investigate the methylation status of the promoter region of the RASSF1A gene in the two groups of patients. RESULTS： For GCA patients, the frequencies of RASSF1A promoter methylation in cancer tissue （CA）, matched dysplasia tissue （DYS） and normal tissue （NOR） were 63.6%, 20% and 4.2%, respectively. For ESCC patients, the frequencies of RASSF1A promoter methylation in tumor tissue, matched dysplasia tissue and normal tissue were 66.7%, 25% and 16.7%, respectively. High methylation frequency was found in both types of cancer tissue. With the evolution of lesions （NOR–DYS-CA）, the frequency of RASSF1A promoter methylation showed an increasing tendency in both GCA （χ^2 = 22.173, P 0.001） and ESCC patients （χ^2 = 19.324, P 0.001）. The frequency of RASSF1A promoter methylation in normal tissue from GCA patients was lower than that from ESCC patients. CONCLUSION： RASSF1A promoter hypermethylation is a molecular event that occurs in both GCA and ESCC patients. RASSF1A is a potential candidate biomarker for early detection of carcinoma of the esophagogastric junction.