RASSF1A 表达的异常甲基化下调与食管癌的进展相关。
Hypermethylation-modulated downregulation of RASSF1A expression is associated with the progression of esophageal cancer.
机构信息
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, PR China.
出版信息
Arch Med Res. 2011 Apr;42(3):182-8. doi: 10.1016/j.arcmed.2011.04.002.
BACKGROUND AND AIMS
Chromosome 3p21 is an important locus harboring critical tumor suppressor genes (TSGs) implicated in the pathogenesis of multiple tumors including esophageal carcinoma (EC). Aberrant promoter methylation is a fundamental mechanism of inactivation of TSGs in cancer. RASSF1A, a candidate tumor suppressor gene, recently cloned from the lung tumor locus at 3p21.3, is frequently inactivated by hypermethylation of its promoter region in a number of malignancies. We undertook this study to investigate the methylation status of RASSF1A and its significance in esophageal squamous cell carcinoma (ESCC).
METHODS
Real-time RT-PCR and real-time methylation-specific PCR (real-time MSP) were used to detect RASSF1A expression and the methylation status of the RASSF1A promoter, respectively, in 124 primary ESCC tissues.
RESULTS
Hypermethylation, partial methylation and unmethylation of the promoter region of RASSF1A were detected in 56 (45.2%), 23 (18.6%) and 45 (36.2%) of 124 ESCC samples, respectively. Unmethylation of the promoter region of RASSF1A was detected in 119 (96%) of the 124 corresponding noncancerous tissues. Five (4.0%) of 124 noncancerous tissues showed partial methylation. The presence of hypermethylation was statistically associated with loss of RASSF1A mRNA expression in primary ESCC (p <0.05). There were statistically significant correlations between the presence of hypermethylation and regional lymph node involvement (p=0.000), histological differentiation (p=0.009) and tumor stage (p=0.000).
CONCLUSIONS
Our results suggest that RASSF1A may be one of the ESCC-related TSGs located at 3p21, and hypermethylation of the CpG island promoter of the RASSF1A is associated with the progression of ESCC.
背景与目的
染色体 3p21 是一个重要的基因座，其中包含多个肿瘤（包括食管癌[EC]）发病机制中关键的肿瘤抑制基因（TSG）。异常启动子甲基化是癌症中 TSG 失活的基本机制。RASSF1A 是从肺肿瘤 3p21.3 基因座克隆的候选肿瘤抑制基因，在许多恶性肿瘤中其启动子区域的高甲基化常导致其失活。我们进行了这项研究，以调查 RASSF1A 的甲基化状态及其在食管鳞状细胞癌（ESCC）中的意义。
方法
采用实时 RT-PCR 和实时甲基化特异性 PCR（实时 MSP）分别检测 124 例原发性 ESCC 组织中 RASSF1A 的表达和 RASSF1A 启动子的甲基化状态。
结果
在 124 例 ESCC 样本中，分别检测到 RASSF1A 启动子区域的高甲基化、部分甲基化和非甲基化 56 例（45.2%）、23 例（18.6%）和 45 例（36.2%）。124 例相应的非癌组织中均检测到 RASSF1A 启动子区域的非甲基化。在 124 例非癌组织中，有 5 例（4.0%）出现部分甲基化。原发性 ESCC 中 RASSF1A 高甲基化与 RASSF1A mRNA 表达缺失具有统计学相关性（p<0.05）。高甲基化的存在与区域淋巴结受累（p=0.000）、组织学分化（p=0.009）和肿瘤分期（p=0.000）显著相关。
结论
我们的研究结果表明，RASSF1A 可能是位于 3p21 的 ESCC 相关 TSG 之一，RASSF1A 启动子 CpG 岛的高甲基化与 ESCC 的进展有关。
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