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高甲基化在胃癌和结直肠癌检测中的作用。

The role of hypermethylation in the detection of gastric and colorectal cancer.

作者信息

Hu Haochang, Chen Xiaoying, Wang Cheng, Jiang Yuting, Li Jingjing, Ying Xiuru, Yang Yong, Li Bin, Zhou Cong, Zhong Jie, Wu Dongping, Ying Jieer, Duan Shiwei

机构信息

Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.

Department of Medical Oncology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Zhejiang 312000, China.

出版信息

Oncotarget. 2017 Sep 20;8(48):84054-84065. doi: 10.18632/oncotarget.21097. eCollection 2017 Oct 13.

Abstract

Gastrointestinal cancer is a prevalent disease with high morbidity and mortality. Tissue factor pathway inhibitor 2 () gene could protect the extracellular matrix of cancer cells from degradation and tumor invasion. The goal of our study was to estimate the diagnostic value of hypermethylation in gastric cancer (GC) and colorectal cancer (CRC). methylation was measured by quantitative methylation-specific polymerase chain reaction (qMSP) method in 114 GC and 80 CRC tissues and their paired non-tumor tissues. Our results showed that methylation was significantly higher in tumor tissues (GC: 29.940% vs. 12.785%, < 0.001; CRC: 26.930% vs. 5.420%, < 0.001). The methylation level of in colorectal tumor tissues was significantly higher than that in colorectal normal tissues (26.930% versus 0.002%, < 0.00001). In GC, hypermethylation yielded an area under the curve (AUC) of 0.762 (95% CI: 0.696-0.828) with a sensitivity of 68% and a specificity of 83%. In CRC, hypermethylation yielded an AUC of 0.759 (95% CI: 0.685-0.834) with a sensitivity of 61% and a specificity of 84%. Similarly, TCGA data also supported hypermethylation was a promising diagnostic marker for GC and CRC. Moreover, the dual-luciferase reporter assay showed fragment could upregulate gene expression (fold change = 5, = 0.005). Data mining further indicated that expression in CRC cell lines was significantly increased after 5'-AZA-deoxycytidine treatment (fold change > 1.37). In conclusion, hypermethylation might be a promising diagnostic biomarker for GC and CRC.

摘要

胃肠道癌症是一种发病率和死亡率都很高的常见疾病。组织因子途径抑制剂2()基因可以保护癌细胞的细胞外基质不被降解以及防止肿瘤侵袭。我们研究的目的是评估高甲基化在胃癌(GC)和结直肠癌(CRC)中的诊断价值。采用定量甲基化特异性聚合酶链反应(qMSP)方法检测了114例GC组织、80例CRC组织及其配对的非肿瘤组织中的甲基化情况。我们的结果显示,肿瘤组织中的甲基化水平显著更高(GC:29.940% 对12.785%,<0.001;CRC:26.930% 对5.420%,<0.001)。结直肠肿瘤组织中的甲基化水平显著高于结直肠正常组织(26.930% 对0.002%,<0.00001)。在GC中,高甲基化产生的曲线下面积(AUC)为0.762(95%可信区间:0.696 - 0.828),敏感性为68%,特异性为83%。在CRC中,高甲基化产生的AUC为0.759(95%可信区间:0.685 - 0.834),敏感性为61%,特异性为84%。同样,TCGA数据也支持高甲基化是GC和CRC的一个有前景的诊断标志物。此外,双荧光素酶报告基因检测显示片段可以上调基因表达(倍数变化 = 5,=0.005)。数据挖掘进一步表明,5'-氮杂脱氧胞苷处理后CRC细胞系中的表达显著增加(倍数变化>1.37)。总之,高甲基化可能是GC和CRC的一个有前景的诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861b/5663576/6d788ccd373c/oncotarget-08-84054-g001.jpg

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