Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serum.
Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serum.
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DOI：
10.1038/sj.bjc.6603721
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发表时间：
2007-04-23
影响因子：
8.8
通讯作者：
Schiller, J. H.
中科院分区：
文献类型：
--
作者：
Belinsky, S. A.;Grimes, M. J.;Casas, E.;Stidley, C. A.;Franklin, W. A.;Bocklage, T. J.;Johnson, D. H.;Schiller, J. H.
5-甲基胞嘧啶去甲基化药物与组蛋白去乙酰化抑制剂联合使用可能为肺癌提供一种新的治疗策略。由于肿瘤的位置，直接在肿瘤内监测基因去甲基化治疗的有效性可能很困难。本研究确定了痰和血清检测肺癌基因甲基化的阳性预测值和阴性预测值。通过将原发肿瘤活检中检测到的甲基化与72例III期肺癌患者的血清和痰进行比较，对一组8个基因进行了评估。痰中8种基因甲基化的发生率(21-43%)与肿瘤相似，但比血清中的甲基化水平高0.7-4.3倍。在对肿瘤活检中基因甲基化状态进行分类时，痰优于血清。前4位基因(p16、DAPK、PAX5、β和GATA5)的阳性预测值为44-72%，⩾的阴性预测值为70%。P16基因的特异性最高，当该基因在痰中甲基化时，肿瘤中甲基化的优势比为6。相比之下，对于血清，个体对所有基因的敏感度为6-27%。评估痰中至少四个最显著基因中的一个甲基化的综合影响将阳性预测值提高到86%。这些研究表明，在活检不可行的情况下，痰可以有效地作为肿瘤组织的替代品来预测晚期肺癌的甲基化状态。
The use of 5-methylcytosine demethylating agents in conjunction with inhibitors of histone deacetylation may offer a new therapeutic strategy for lung cancer. Monitoring the efficacy of gene demethylating treatment directly within the tumour may be difficult due to tumour location. This study determined the positive and negative predictive values of sputum and serum for detecting gene methylation in primary lung cancer. A panel of eight genes was evaluated by comparing methylation detected in the primary tumour biopsy to serum and sputum obtained from 72 patients with Stage III lung cancer. The prevalence for methylation of the eight genes in sputum (21–43%) approximated to that seen in tumours, but was 0.7–4.3-fold greater than detected in serum. Sputum was superior to serum in classifying the methylation status of genes in the tumour biopsy. The positive predictive value of the top four genes (p16, DAPK, PAX5 β, and GATA5) was 44–72% with a negative predictive value for these genes ⩾70%. The highest specificity was seen for the p16 gene, and this was associated with a odds ratio of six for methylation in the tumour when this gene was methylated in sputum. In contrast, for serum, the individual sensitivity for all genes was 6–27%. Evaluating the combined effect of methylation of at least one of the four most significant genes in sputum increased the positive predictive value to 86%. These studies demonstrate that sputum can be used effectively as a surrogate for tumour tissue to predict the methylation status of advanced lung cancer where biopsy is not feasible.
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影响因子：
11.5
作者：
Belinsky, SA;Klinge, DM;Picchi, MA
通讯作者：
Picchi, MA
影响因子：
11.5
作者：
Guo, MZ;House, MG;Brock, MV
通讯作者：
Brock, MV
影响因子：
11.2
作者：
Yang, Allen S.;Doshi, Ketan D.;Issa, Jean-Pierre J.
通讯作者：
Issa, Jean-Pierre J.
影响因子：
30.8
作者：
Cameron, EE;Bachman, KE;Baylin, SB
通讯作者：
Baylin, SB
DOI：
10.1073/pnas.95.20.11891
发表时间：
1998-09-29
影响因子：
11.1
作者：
Belinsky, SA;Nikula, KJ;Herman, JG
通讯作者：
Herman, JG