Mizukami Hiroki, Shirahata Atsushi, Goto Tetsuhiro, Sakata Makiko, Saito Mitsuo, Ishibashi Kazuyoshi, Kigawa Gaku, Nemoto Hiroshi, Sanada Yutaka, Hibi Kenji
Department of Surgery, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan.
Anticancer Res. 2008 Sep-Oct;28(5A):2697-700.
Recently, it has been proven that protein gene product 9.5 (PGP9.5) hypomethylation might play an important role in re-expression of the PGP9.5 gene in gallbladder cancer. We previously examined the expression of PGP9.5 in primary colorectal cancer using immunohistochemistry and found that PGP9.5 expression is related to tumor progression and may be useful as a marker for invasive colorectal cancer. These results prompted us to examine the methylation status of the PGP9.5 gene in colorectal cancer.
The methylation status of the PGP9.5 gene in primary tumors derived from 49 patients with colorectal cancer using a quantitative methylation-specific polymerase chain reaction (qMSP) and the association between the methylation status and the clinicopathological findings was evaluated.
An aberrant methylation of the PGP9.5 gene was detected in 36 out of 49 (73%) primary colon cancer samples. Subsequently, clinicopathological data were tested for their association with the methylation results. Lymph node metastasis was significantly associated with a lower frequency of methylation (p=0.029).
These findings indicated that PGP9.5 was less frequently methylated in metastatic colorectal cancer, suggesting that PGP9.5 hypomethylation might play an important role in re-expression of the PGP9.5 gene in colorectal cancer.
最近,已证实蛋白基因产物9.5(PGP9.5)的低甲基化可能在胆囊癌中PGP9.5基因的重新表达中起重要作用。我们之前使用免疫组织化学检测了原发性结直肠癌中PGP9.5的表达,发现PGP9.5表达与肿瘤进展相关,并且可能作为浸润性结直肠癌的标志物。这些结果促使我们检测结直肠癌中PGP9.5基因的甲基化状态。
使用定量甲基化特异性聚合酶链反应(qMSP)评估49例结直肠癌患者原发性肿瘤中PGP9.5基因的甲基化状态,并评估甲基化状态与临床病理结果之间的关联。
在49例原发性结肠癌样本中的36例(73%)中检测到PGP9.5基因的异常甲基化。随后,检测临床病理数据与甲基化结果的相关性。淋巴结转移与较低的甲基化频率显著相关(p=0.029)。
这些发现表明,PGP9.5在转移性结直肠癌中的甲基化频率较低,提示PGP9.5低甲基化可能在结直肠癌中PGP9.5基因的重新表达中起重要作用。