Xu Zhiying, Chen Hui, Liu Deliang, Huo Jirong
From the Department of Gastroenterology (ZX, DL, JH), 2nd Xiangya Hospital, Central South University, Changsha, Hunan; and Department of Gastroenterology (ZX, HC), People's Hospital of Taizhou, Taizhou, Jiangsu, China.
Medicine (Baltimore). 2015 Apr;94(13):e663. doi: 10.1097/MD.0000000000000663.
Fibulin-1 (FBLN1) is involved in the progression of some types of cancer. However, the role of FBLN1 in colorectal cancer (CRC) has not been examined. The purpose of this study was to understand the molecular mechanisms and clinical significance of FBLN1 inactivation in CRC. The expression of FBLN1 in CRC tissues and adjacent normal tissues was analyzed by immunohistochemical analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Methylation-specific polymerase chain reaction (MSP) and bisulfite sequencing PCR (BSP) were performed to examine the methylation status of the FBLN1 gene promoter. Furthermore, the methylated level of FBLN1 was analyzed with the clinicopathological characteristics. Immunohistochemical analysis and qRT-PCR analysis showed that FBLN1 protein and messenger RNA (mRNA) levels in tumor tissues were both significantly decreased compared with that in adjacent nontumor tissues. The methylation rate of FBLN1 promoter was significantly higher in CRC tissues than that in adjacent nontumor tissues (P < 0.001). In addition, the correlation between FBLN1 hypermethylation, protein expression, and overall survival (OS) was statistically significant. Our results indicated that the FBLN1 gene may be a novel candidate of tumor suppressor gene in CRC, and that promoter hypermethylation of FBLN1 is an important reason for its downregulation and is also a good predictor of OS for CRC.
纤连蛋白-1（FBLN1）参与某些类型癌症的进展。然而，FBLN1在结直肠癌（CRC）中的作用尚未得到研究。本研究的目的是了解FBLN1失活在CRC中的分子机制和临床意义。通过免疫组织化学分析和定量实时聚合酶链反应（qRT-PCR）分析CRC组织和相邻正常组织中FBLN1的表达。进行甲基化特异性聚合酶链反应（MSP）和亚硫酸氢盐测序PCR（BSP）以检测FBLN1基因启动子的甲基化状态。此外，分析FBLN1的甲基化水平与临床病理特征的关系。免疫组织化学分析和qRT-PCR分析表明，与相邻非肿瘤组织相比，肿瘤组织中FBLN1蛋白和信使核糖核酸（mRNA）水平均显著降低。CRC组织中FBLN1启动子的甲基化率显著高于相邻非肿瘤组织（P<0.001）。此外，FBLN1高甲基化、蛋白表达与总生存期（OS）之间的相关性具有统计学意义。我们的结果表明，FBLN1基因可能是CRC中一种新发现的肿瘤抑制基因候选者，FBLN1启动子高甲基化是其下调的重要原因，也是CRC患者OS的良好预测指标。
