Comprehensive analysis identifying aberrant DNA methylation in rectal mucosa from ulcerative colitis patients with neoplasia.
Comprehensive analysis identifying aberrant DNA methylation in rectal mucosa from ulcerative colitis patients with neoplasia.
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DOI：
10.18632/oncotarget.26032
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发表时间：
2018-09-04
期刊：
影响因子：
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通讯作者：
Kusunoki M
中科院分区：
文献类型：
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作者：
Toiyama Y;Okugawa Y;Kondo S;Okita Y;Araki T;Kusunoki K;Uchino M;Ikeuchi H;Hirota S;Mitsui A;Takehana K;Umezawa T;Kusunoki M
目前还没有生物标志物来帮助识别溃疡性结肠炎(UC)患者谁是发展为结直肠癌(CRC)的高危人群。在我们目前的研究中，我们使用UC患者的直肠组织来识别异常的DNA甲基化，并评估它们是否可以用于识别UC患者合并大肠肿瘤。使用训练集，我们使用CHAMP算法在直肠粘膜中识别了484个具有绝对增量β值的差异甲基化区域(DMRS)。接下来，使用484个DMR进行通路富集化分析，以选择协同甲基化的DMR，从而在UC-CRC的直肠组织中选择187个异常DMR。然后，采用弹性网络分类算法对最优变异DMRS进行筛选，最终筛选出11个DMR作为UC-CRC患者的生物标志物。选择的11个DMRS可以在训练集(曲线下面积0.96)和验证集(曲线下面积0.81)中区分有或没有结直肠癌的UC患者。总之，我们确定了11个可以识别UC患者合并结直肠癌并发症的DMR。前瞻性研究应进一步证实这些生物标志物的有效性。我们对24例UC-CRC和24例训练组UC患者的直肠粘膜组织(n=48)进行了全基因组DNA甲基化分析。接下来，我们对8例UC-CRC和8例UC患者的直肠粘膜组织(n=16)进行了全面的DNA甲基化分析以进行验证。
There are no biomarkers to facilitate the identification of patients with ulcerative colitis (UC) who are at high risk for developing colorectal cancer (CRC). In our current study, we used rectal tissues from UC patients to identify aberrant DNA methylations and evaluated whether they could be used to identify UC patients with coexisting colorectal neoplasia. Using a training set, we identified 484 differentially methylated regions (DMRs) with absolute delta beta-values > 0.1 in rectal mucosa by using the ChAMP algorithm. Next, pathway enrichment analysis was performed using 484 DMRs to select coordinately methylated DMRs, resulting in the selection of 187 aberrant DMRs in rectal tissues from UC-CRC. Then, the Elastic Net classification algorithm was performed to narrow down optimal aberrant DMRs, and we finally selected 11 DMRs as biomarkers for identification of UC-CRC patients. The 11 chosen DMRs could discriminate UC patients with or without CRC in a training set (area under the curve, 0.96) and the validation set (area under the curve, 0.81). In conclusion, we identified 11 DMRs that could identify UC patients with CRC complications. Prospective studies should further confirm the validity of these biomarkers. We performed genome-wide DNA methylation profiles in rectal mucosal tissues (n = 48) from 24 UC-CRC and 24 UC patients in a training set. Next, we performed comprehensive DNA methylation analysis using rectal mucosal tissues (n = 16) from 8 UC-CRC and 8 UC patients for validation.