Promoter hypermethylation of the tumor-suppressor genes ITIH5, DKK3, and RASSF1A as novel biomarkers for blood-based breast cancer screening.
Promoter hypermethylation of the tumor-suppressor genes ITIH5, DKK3, and RASSF1A as novel biomarkers for blood-based breast cancer screening.
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DOI：
10.1186/bcr3375
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发表时间：
2013-01-15
期刊：
影响因子：
--
通讯作者：
Dahl E
中科院分区：
文献类型：
--
作者：
Kloten V;Becker B;Winner K;Schrauder MG;Fasching PA;Anzeneder T;Veeck J;Hartmann A;Knüchel R;Dahl E
对于乳腺癌的早期检测，开发能够准确反映宿主肿瘤的血液生物标记物是必要的。我们研究了乳腺癌患者和配对对照血液中循环游离DNA(CfDNA)中的DNA甲基化，以建立一个可能有助于乳腺癌早期检测的生物标志物小组。我们检测了从血清中提取的cfDNA中七个可能的肿瘤抑制基因(SFRP1、SFRP2、SFRP5、ITIH5、WIF1、DKK3和RASSF1A)的启动子甲基化。临床表现首先在测试集(n=261份血清)中确定。在一个独立的验证集(n=343份血清)中，我们验证了最有希望进一步用于早期乳腺癌检测的基因。59例良性乳腺疾病和58例结肠癌患者的血清被纳入额外的特异性测试。基于测试集，我们将ITIH5和DKK3启动子甲基化确定为灵敏度和特异度最高的候选生物标志物。在测试和验证组合中，ITIH5和DKK3甲基化在健康对照和良性疾病对照中分别达到41%的敏感性和93%的特异性和100%的特异性。结合这些基因和RASSF1A甲基化，在健康对照组和良性疾病对照组中，敏感性提高到67%，特异性分别为69%和82%。三基因组(ITIH5、DKK3和RASSF1A)的肿瘤特异性甲基化可能是乳腺癌早期检测的有价值的生物标记物。
For early detection of breast cancer, the development of robust blood-based biomarkers that accurately reflect the host tumor is mandatory. We investigated DNA methylation in circulating free DNA (cfDNA) from blood of breast cancer patients and matched controls to establish a biomarker panel potentially useful for early detection of breast cancer. We examined promoter methylation of seven putative tumor-suppressor genes (SFRP1, SFRP2, SFRP5, ITIH5, WIF1, DKK3, and RASSF1A) in cfDNA extracted from serum. Clinical performance was first determined in a test set (n = 261 sera). In an independent validation set (n = 343 sera), we validated the most promising genes for further use in early breast cancer detection. Sera from 59 benign breast disease and 58 colon cancer patients were included for additional specificity testing. Based on the test set, we determined ITIH5 and DKK3 promoter methylation as candidate biomarkers with the best sensitivity and specificity. In both the test and validation set combined, ITIH5 and DKK3 methylation achieved 41% sensitivity with a specificity of 93% and 100% in healthy and benign disease controls, respectively. Combination of these genes with RASSF1A methylation increased the sensitivity to 67% with a specificity of 69% and 82% in healthy controls and benign disease controls, respectively. Tumor-specific methylation of the three-gene panel (ITIH5, DKK3, and RASSF1A) might be a valuable biomarker for the early detection of breast cancer.
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影响因子：
2.6
作者：
Brooks, Jennifer D.;Cairns, Paul;Shore, Roy E.;Klein, Catherine B.;Wirgin, Isaac;Afanasyeva, Yelena;Zeleniuch-Jacquotte, Anne
通讯作者：
Zeleniuch-Jacquotte, Anne
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
4.7
作者：
Ai, Lingbao;Tao, Qian;Robertson, Keith D.
通讯作者：
Robertson, Keith D.
DOI：
10.1093/jnci/87.21.1622
发表时间：
1995-11-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
BYRNE, C;SCHAIRER, C;HAILE, R
通讯作者：
HAILE, R
DOI：
10.1093/jnci/92.13.1081
发表时间：
2000-07-05
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Mandelson, MT;Oestreicher, N;White, E
通讯作者：
White, E