Huang Jin, Tan Zhi-Rong, Yu Jing, Li He, Lv Qiao-Li, Shao Ying-Ying, Zhou Hong-Hao
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan.
Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan.
Onco Targets Ther. 2017 Sep 26;10:4739-4751. doi: 10.2147/OTT.S143389. eCollection 2017.
Colorectal cancer (CRC) is a widespread and aggressive carcinoma with poor prognosis. Hypermethylation of specific gene promoters is an important mechanism of CRC. In this study, we investigated the hypermethylation of paired boxed gene 1 () and sex-determining region Y-related high-mobility group box 1 () genes in CRC tissues.
DNA methylation at cg2,09,07,471 and cg0,66,75,478 from 166 cancer tissues and 37 normal tissues from CRC patients were compared using datasets downloaded from The Cancer Genome Atlas. Quantitative methylation-specific polymerase chain reaction and assay of and were performed in dissected tumor and paracancerous tissues by surgery from 41 CRC patients. Quantitative reverse transcription polymerase chain reaction and immunohistochemistry assay were performed in both CRC and paired normal tissues to detect mRNA and protein expression, respectively.
Methylation levels of / genes were significantly higher in cancer tissues than in paired normal tissues. and genes were methylated in 28 (68.3%) of the 41 CRC samples but in 5 (12.2%) and 0 (0%) of the paired normal control samples (both <0.001), respectively. Sensitivities and specificities of methylation for the detection of cancer were 68.3% and 87.8%, respectively, whereas the corresponding values for were 68.3% and 100%. However, the Kaplan-Meier analysis illustrated no significant difference in the overall survivals between patients with high and low methylation levels of or (>0.5). In addition, the methylation level of / was significantly higher in CRC patients with high TNM stage (TNM stage III/IV, 3.11±2.43) than those with low TNM stage (TNM stage I/II, 1.26±2.94, <0.05). Relative RNA and protein expression levels of / were both significantly lower in CRC tissues than in their paired normal tissue.
This study is the first analysis of the methylation of /, which may be new biomarkers for CRC screening.
结直肠癌（CRC）是一种广泛存在且侵袭性强、预后较差的癌症。特定基因启动子的高甲基化是CRC的重要机制。在本研究中，我们调查了结直肠癌组织中配对盒基因1（）和性别决定区Y相关高迁移率族盒1（）基因的高甲基化情况。
使用从癌症基因组图谱下载的数据集，比较了166例CRC患者癌组织和37例正常组织中cg2,09,07,471和cg0,66,75,478处的DNA甲基化情况。对41例CRC患者手术切除的肿瘤组织和癌旁组织进行了定量甲基化特异性聚合酶链反应以及和的检测。在CRC组织及其配对的正常组织中分别进行定量逆转录聚合酶链反应和免疫组化检测，以检测mRNA和蛋白质表达。
癌组织中/基因的甲基化水平显著高于配对的正常组织。41例CRC样本中有28例（68.3%）的和基因发生甲基化，而配对的正常对照样本中分别有5例（12.2%）和0例（0%）发生甲基化（均<0.001）。甲基化检测癌症的敏感性和特异性分别为68.3%和87.8%，而的相应值分别为68.3%和100%。然而，Kaplan-Meier分析表明，和甲基化水平高与低的患者总体生存率无显著差异（>0.5）。此外，TNM分期高（TNM分期III/IV，3.11±2.43）的CRC患者中/的甲基化水平显著高于TNM分期低（TNM分期I/II，1.26±2.94，<0.05）的患者。CRC组织中/的相对RNA和蛋白质表达水平均显著低于其配对的正常组织。
本研究首次分析了/的甲基化情况，其可能是CRC筛查的新生物标志物。
