Liu He, Li Yongmin, Li Jingwen, Liu Yanlong, Cui Binbin
Department of Colorectal Surgery, Harbin Medical University, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China.
Oncol Lett. 2018 Aug;16(2):2125-2134. doi: 10.3892/ol.2018.8902. Epub 2018 Jun 5.
Histone methylation is closely associated with the occurrence of cancer. Histone H3 trimethylation at lysine 4 (H3K4me3) has been reported to modulate the expression of tumor-associated expression and be altered during the progression of several human cancers. WD Repeat Domain 82 (Wdr82), a key epigenetics-associated factor, is a component of the H3K4me3 methyltransferase complex. An aim of the present study was to determine H3K4me3 and Wdr82 expression and their clinical significances in colorectal cancer (CRC). Immunohistochemistry results demonstrated that the expression level of the H3K4me3 and Wdr82 were significantly decreased in CRC tissues compared with paired noncancerous tissues from 123 patients with CRC. Furthermore, the negative expression of H3K4me3 and Wdr82 expression were significantly associated with lymph node (n=33, P=0.0001) and liver metastasis (n=30, P=0.0001). Additionally, multivariate Cox regression analysis indicated that the low expression level of H3K4me3 or Wdr82 was associated with reduced overall survival (OS, P<0.05), and patients with a low H3K4me3 and Wdr82 expression had a significantly poorer outcome compared with patients with a high expression of H3K4me3 and Wdr82 (P=0.0001), suggesting that H3K4me3 and Wdr82 expression were independent factors for OS in patients with CRC. In conclusion, the decreased expressions of H3K4me3 and Wdr82 were associated with a poor prognosis in CRC. The combined expression of H3K4me3 and Wdr82 may serve as a novel prognostic marker for CRC.
组蛋白甲基化与癌症的发生密切相关。据报道，赖氨酸4位点的组蛋白H3三甲基化（H3K4me3）可调节肿瘤相关基因的表达，并且在几种人类癌症的进展过程中会发生改变。WD重复结构域82（Wdr82）是一种关键的表观遗传学相关因子，是H3K4me3甲基转移酶复合物的一个组成部分。本研究的目的是确定H3K4me3和Wdr82在结直肠癌（CRC）中的表达及其临床意义。免疫组织化学结果显示，与123例CRC患者的配对癌旁组织相比，CRC组织中H3K4me3和Wdr82的表达水平显著降低。此外，H3K4me3和Wdr82的阴性表达与淋巴结转移（n = 33，P = 0.0001）和肝转移（n = 30，P = 0.0001）显著相关。此外，多因素Cox回归分析表明，H3K4me3或Wdr82的低表达水平与总生存期（OS）降低相关（P < 0.05），与H3K4me3和Wdr82高表达的患者相比，H3K4me3和Wdr82低表达的患者预后明显更差（P = 0.0001），这表明H3K4me3和Wdr82的表达是CRC患者OS的独立影响因素。总之，H3K4me3和Wdr82表达降低与CRC预后不良相关。H3K4me3和Wdr82的联合表达可能作为CRC的一种新的预后标志物。
