Wu Jie, Wang Guangchuan, He Baojun, Chen Xuejun, An Yuzhi
1 Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
2 Department of Immunology, School of Basic Medical Science, Jinzhou Medical University, Jinzhou, China.
Tumour Biol. 2017 Apr;39(4):1010428317697564. doi: 10.1177/1010428317697564.
UNC5C is a member of the UNC5H family of transmembrane receptors and functions as a dependence receptor. The expression of UNC5C is lost or markedly reduced in a large proportion of cancers at the messenger RNA level. However, there is little information available regarding the protein expression of UNC5C, the relationship between UNC5C protein expression and UNC5C methylation, and the correlation between patient clinical features and UNC5C protein expression in colorectal cancer. In this study, the methylation and protein expression of UNC5C were examined in 36 adenomatous polyps, 73 colorectal cancers, and 28 corresponding normal mucosa, and the correlation between the methylation, as well as protein expression status, and the clinicopathologic features was evaluated. Furthermore, the relationship between the methylation and protein expression of UNC5C, and correlation between UNC5C protein expression and overall survival were analyzed. The results showed that aberrant methylation of UNC5C was observed in colorectal cancers (78%) and adenomatous polyps (64%). The methylation-specific polymerase chain reaction results were confirmed by bisulfite sequencing of UNC5C promoter region. UNC5C methylation was significantly higher in early tumor, node, metastasis stage (I + II) of colorectal cancers. Compared with the corresponding normal tissues, protein expression of UNC5C was significantly lower in colorectal cancers (42%) and adenomatous polyps (81%). Protein expression of UNC5C was significantly higher in early tumor, node, metastasis stage (I + II) of colorectal cancers compared with advanced tumor, node, metastasis stage. Furthermore, patients with UNC5C-negative expression had a poorer prognosis than those with UNC5C-positive expression through Kaplan-Meier survival analysis ( p = 0.038), univariate ( p = 0.044) and multivariate analysis ( p = 0.045). According to Spearman rank correlation analysis, UNC5C methylation and protein expression were negatively correlated ( r = -0.461, p < 0.001). Together, these results suggest that UNC5C methylation may be an earlier event in the development of colorectal cancer, which was negatively correlated with protein expression. UNC5C may have a critical role in the pathogenesis of colorectal cancers and be a valuable prognostic factor of colorectal cancers patients. UNC5C may be identified as an attractive therapeutic target for the treatment of colorectal cancers in the further studies.
UNC5C是跨膜受体UNC5H家族的成员，作为一种依赖受体发挥作用。在大多数癌症中，UNC5C在信使RNA水平上的表达缺失或显著降低。然而，关于UNC5C的蛋白质表达、UNC5C蛋白质表达与UNC5C甲基化之间的关系，以及结直肠癌患者临床特征与UNC5C蛋白质表达之间的相关性，目前可用信息较少。在本研究中，检测了36例腺瘤性息肉、73例结直肠癌和28例相应正常黏膜中UNC5C的甲基化和蛋白质表达，并评估了甲基化、蛋白质表达状态与临床病理特征之间的相关性。此外，分析了UNC5C甲基化与蛋白质表达之间的关系，以及UNC5C蛋白质表达与总生存期之间的相关性。结果显示，在结直肠癌（78%）和腺瘤性息肉（64%）中观察到UNC5C的异常甲基化。通过UNC5C启动子区域的亚硫酸氢盐测序证实了甲基化特异性聚合酶链反应结果。在结直肠癌的早期肿瘤、淋巴结、转移分期（I+II期）中，UNC5C甲基化显著更高。与相应正常组织相比，结直肠癌（42%）和腺瘤性息肉（81%）中UNC5C的蛋白质表达显著更低。与晚期肿瘤、淋巴结、转移分期相比，结直肠癌早期肿瘤、淋巴结、转移分期（I+II期）中UNC5C蛋白表达显著更高。此外，通过Kaplan-Meier生存分析（p=0.038）、单因素分析（p=0.044）和多因素分析（p=0.045），UNC5C阴性表达的患者预后比UNC5C阳性表达的患者更差。根据Spearman等级相关分析，UNC5C甲基化与蛋白质表达呈负相关（r=-0.461，p<0.001）。总之，这些结果表明，UNC5C甲基化可能是结直肠癌发生发展中的一个早期事件，与蛋白质表达呈负相关。UNC5C可能在结直肠癌的发病机制中起关键作用，是结直肠癌患者的一个有价值的预后因素。在进一步研究中，UNC5C可能被确定为结直肠癌治疗的一个有吸引力的治疗靶点。
