Novel target genes and a valid biomarker panel identified for cholangiocarcinoma.
Novel target genes and a valid biomarker panel identified for cholangiocarcinoma.
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新型靶基因和针对胆管癌鉴定的有效生物标志物面板。
DOI：
10.4161/epi.22191
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发表时间：
2012-11
期刊：
影响因子：
3.7
通讯作者：
Lind GE
中科院分区：
文献类型：
--
作者：
Andresen K;Boberg KM;Vedeld HM;Honne H;Hektoen M;Wadsworth CA;Clausen OP;Karlsen TH;Foss A;Mathisen O;Schrumpf E;Lothe RA;Lind GE
胆管癌是出了名的难以诊断，并且由于晚期临床表现，死亡率很高。CpG岛启动子甲基化在癌症发展中常见。在本研究中，我们的目的是确定新的表观遗传生物标志物的潜力，以提高诊断准确性的胆管癌。将用表观遗传药物治疗的胆管癌细胞系及其未治疗的对应物的微阵列数据分析与先前发表的原发性肿瘤的基因表达谱和非恶性对照进行比较。与对照组（n = 43）相比，原发性胆管癌中对表观遗传治疗同时下调的基因在胃肠道癌细胞系中的启动子甲基化状态进行了研究。对胆管癌细胞系中常见的甲基化基因进行定量甲基化特异性聚合酶链反应，共93个临床样本（胆管癌和非恶性对照）。CDO1、DCLK1、SFRP 1和ZSCAN18在原发性肿瘤中显示高甲基化频率，而在对照中未甲基化。这四种生物标志物中至少有一种在87%的肿瘤样本中呈阳性，特异性为100%。总之，新的基于甲基化的生物标志物组显示出对胆管癌的高灵敏度和特异性。这些标记物在早期诊断这种癌症类型中的潜力应进一步探索。
Cholangiocarcinoma is notoriously difficult to diagnose, and the mortality rate is high due to late clinical presentation. CpG island promoter methylation is frequently seen in cancer development. In the present study, we aimed at identifying novel epigenetic biomarkers with the potential to improve the diagnostic accuracy of cholangiocarcinoma. Microarray data analyses of cholangiocarcinoma cell lines treated with epigenetic drugs and their untreated counterparts were compared with previously published gene expression profiles of primary tumors and with non-malignant controls. Genes responding to the epigenetic treatment that were simultaneously downregulated in primary cholangiocarcinoma compared with controls (n = 43) were investigated for their promoter methylation status in cancer cell lines from the gastrointestinal tract. Genes commonly methylated in cholangiocarcinoma cell lines were subjected to quantitative methylation-specific polymerase chain reaction in a total of 93 clinical samples (cholangiocarcinomas and non-malignant controls). CDO1, DCLK1, SFRP1 and ZSCAN18, displayed high methylation frequencies in primary tumors and were unmethylated in controls. At least one of these four biomarkers was positive in 87% of the tumor samples, with a specificity of 100%. In conclusion, the novel methylation-based biomarker panel showed high sensitivity and specificity for cholangiocarcinoma. The potential of these markers in early diagnosis of this cancer type should be further explored.
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影响因子：
1.9
作者：
Boberg, KM;Bergquist, A;Schrumpf, E
通讯作者：
Schrumpf, E
影响因子：
3.7
作者：
Gonzalo, Victoria;Jose Lozano, Juan;Castells, Antoni
通讯作者：
Castells, Antoni
鉴定对结直肠癌和腺瘤具有高灵敏度和特异性的表观遗传生物标记物面板。
影响因子：
37.3
作者：
Lind GE;Danielsen SA;Ahlquist T;Merok MA;Andresen K;Skotheim RI;Hektoen M;Rognum TO;Meling GI;Hoff G;Bretthauer M;Thiis-Evensen E;Nesbakken A;Lothe RA
通讯作者：
Lothe RA
影响因子：
11.2
作者：
Lodygin, D;Epanchintsev, A;Hermeking, H
通讯作者：
Hermeking, H
影响因子：
4.6
作者：
Luna, Laura E. Moreno;Gores, Gregory J.
通讯作者：
Gores, Gregory J.