DNA integrity assay: A plasma-based screening tool for the detection of prostate cancer

DNA integrity assay: A plasma-based screening tool for the detection of prostate cancer
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DOI:
10.1158/1078-0432.ccr-06-0130
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发表时间:
2006-08-01
影响因子:
11.5
通讯作者:
Summerhayes, Ian C.
Summerhayes, Ian C.
中科院分区:
医学1区
文献类型:
--
作者:
Hanley, Robert;Rieger-Christ, Kimberly M.;Summerhayes, Ian C.

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目的:本研究的目的是评估的DNA完整性测定(DIA)作为血浆为基础的筛选工具,用于检测前列腺癌的实用性。实验设计:血液样本收集活检证实前列腺癌患者前列腺切除术前(n = 123)和两个自旋血浆制剂处理。三个对照组包括:男性(40岁,无癌症史)(第1组,n = 20);无癌症的前列腺切除术后患者(第2组,n = 25)和前列腺活检阴性的患者(第3组,n = 22)。分离血浆制剂中的DNA,杂交捕获,并在实时PCR中多重化DNA片段(200 bp、1.3、1.8和2.4 kb)。结果:前列腺癌患者(123例中的86例; 69.9%)被确定为具有>= 7的阳性DIA评分。对照组1、2和3的DIA结果显示特异性分别为90%、92%和68.2%。在年龄校正的前列腺特异性抗原(PSA)阴性和前列腺癌的患者中,30例中有19例(63%)DIA评分阳性。DIA的受试者工作特征曲线下面积为0.788。结论:DIA对前列腺癌的检出率为69.9%,总体特异性为68.2%~ 92%,与目前公认的PSA的特异性范围(60-70%)相当。对照组之间特异性的变异性可能通过与对照组3相关的后续活检中确定的19%至30%的前列腺癌检测来解释。DIA检测到63%的前列腺癌未被目前公认的PSA范围检测到。
Purpose: The aim of this study was to evaluate the utility of the DNA integrity assay (DIA) as a plasma-based screening tool for the detection of prostate cancer.Experimental Design: Blood samples were collected from patients with biopsy-proven prostate cancer prior to prostatectomy (n = 123) and processed as two-spin plasma preparations. The three control groups included: males (40 years old with no history of cancer (group 1, n = 20); cancer-free postprostatectomy patients (group 2, n = 25), and patients with a negative prostate biopsy (group 3, n = 22). DNA in plasma preparations were isolated, hybrid-captured, and DNA fragments (200 bp, 1.3,1.8, and 2.4 kb) were multiplexed in real-time PCR. A baseline cutoff was determined for individual fragment lengths to establish a DIA score for each patient sample.Results: Patients with prostate cancer (86 of 123; 69.9%) were determined to have a positive DIA score of >= 7. The DIA results from control groups 1, 2, and 3 showed specificities of 90%, 92%, and 68.2%, respectively. Of the patients with negative age-adjusted prostate-specific antigen (PSA) and prostate cancer, 19 of 30 (63%) had a positive DIA score. The area under the receiver operating characteristic curve for DIA was 0.788.Conclusion: While detecting 69.9% of those with prostate cancer, DIA maintained an overall specificity of 68.2% to 92%, a range favorably comparable to that currently accepted for PSA (60-70%). The variability in specificity between control groups is likely explained by the established 19% to 30% detection of prostate cancer on subsequent biopsies associated with control group 3. DIA detected 63% of the prostate cancers undetected by currently accepted PSA ranges.