Increased plasma DNA integrity in cancer patients.

Increased plasma DNA integrity in cancer patients.
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DOI:
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发表时间:
2003-07
期刊:
影响因子:
11.2
通讯作者:
Brant G Wang;Han-Yao Huang;Yu-Chi Chen;R. Bristow;Keyanunoosh Kassauei;C. Cheng;R. Roden;L. Sokoll-L.
Brant G Wang;Han-Yao Huang;Yu-Chi Chen;R. Bristow;Keyanunoosh Kassauei;C. Cheng;R. Roden;L. Sokoll-L.
中科院分区:
医学1区
文献类型:
--
作者:
Brant G Wang;Han-Yao Huang;Yu-Chi Chen;R. Bristow;Keyanunoosh Kassauei;C. Cheng;R. Roden;L. Sokoll-L.

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血液中肿瘤释放的 DNA 是一种很有前景的癌症检测生物标志物。据推测,肿瘤坏死会导致不同大小的 DNA 释放,这与正常组织中释放更小且更均匀的 DNA 片段的细胞凋亡形成鲜明对比。为了检验 DNA 完整性增加(即更长的 DNA 链)是血浆中肿瘤相关标志物的假设,我们使用实时 PCR 测定确定了血浆 DNA 中的基因组 DNA 完整性指数。研究人员测定了 61 名妇科癌症和乳腺癌患者以及 65 名无肿瘤疾病的女性患者的 DNA 完整性指数和血浆 DNA 浓度。我们发现癌症患者与非肿瘤患者的 DNA 完整性指数接受者操作特征曲线下面积为 0.911。考虑到 100% 的特异性,在指数截止值为 0.59 时,检测癌症组的最高灵敏度为 62%(95% 置信区间 = 0.50-0.74)。百分之五十的 I 期癌症的 DNA 完整性指数高于此界限。所有 11 例临床上可能与妇科恶性肿瘤相混淆的良性附件肿块患者的 DNA 完整性指数均 < 0.59。我们的研究结果表明,血浆 DNA 中 DNA 完整性的增加与癌症相关,DNA 完整性的测量可能为癌症检测提供一种简单且廉价的方法。
Tumor-released DNA in blood represents a promising biomarker for cancer detection. It has been postulated that tumor necrosis causes release of DNA of varying sizes, which contrasts apoptosis in normal tissue that releases smaller and more uniform DNA fragments. To test the hypothesis that increased DNA integrity, i.e., a longer DNA strand, is a tumor-associated marker in plasma, we determined the genomic DNA integrity index in plasma DNA using real-time PCR assays. A DNA integrity index and DNA concentration in plasma were determined in 61 patients with gynecological and breast cancers and 65 female patients without neoplastic diseases. We found that the area under the receiver-operating characteristic curve for DNA integrity index was 0.911 for cancer versus nonneoplastic patients. Given 100% specificity, the highest sensitivity achieved in detecting the cancer group was 62% (95% confidence interval = 0.50-0.74) at the index cutoff of 0.59. Fifty percent of stage I cancers had a DNA integrity index above this cutoff. All 11 patients with benign adnexal masses that clinically can be confused with malignant gynecological neoplasms demonstrated DNA integrity index < 0.59. Our findings suggest that increased DNA integrity in plasma DNA is associated with cancer, and measurement of DNA integrity may provide a simple and inexpensive measure for cancer detection.