Bastian Patrick J, Palapattu Ganesh S, Yegnasubramanian Srinivasan, Lin Xiaohui, Rogers Craig G, Mangold Leslie A, Trock Bruce, Eisenberger Mario, Partin Alan W, Nelson William G
The James Buchanan Brady Urological Institute, Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5361-7. doi: 10.1158/1078-0432.CCR-06-2781.
We evaluated the association of preoperative serum cell-free circulating DNA concentration in men with clinically localized prostate cancer who underwent radical prostatectomy with prostate-specific antigen (PSA) recurrence.
One hundred and ninety-two men with clinically localized prostate cancer, who underwent radical prostatectomy at the Johns Hopkins Hospital and had preoperative serum available for analyses constituted our study population. All serum samples were collected before prostate biopsy or at least 4 months after prostate biopsy. The total amount of serum cell-free circulating DNA from each sample was calculated using a standard curve generated via quantitative real-time PCR. PSA recurrence was defined as a single postoperative PSA level of > or =0.2. The natural logarithm (ln) of the DNA concentration was used for statistical analyses.
Of the 192 men in our study, 56 (29%) experienced PSA recurrence within the study period (median time to PSA recurrence 2 years). The median follow-up time for men free of disease at last follow-up was 3 years. The median serum cell-free DNA concentration of all men in the study was 5.3 ng/mL (mean 18.05 ng/mL; range 0.2-320 ng/mL). The mean serum DNA concentration for men who recurred and for those who did not was 3.8 +/- 34.1 and 13.7 +/- 33.6 ng/mL, respectively (P = 0.001). In a univariate analysis, ln DNA concentration was significantly associated with PSA recurrence (hazard ratio, 1.49; 95% confidence interval, 1.3-1.8; P < 0.001). In the multivariate model, ln DNA concentration was significantly associated with PSA recurrence (hazard ratio, 2.56; 95% confidence interval, 1.1-1.6; P = 0.003). Using bootstrap analyses, serum cell-free DNA concentrations > or =5.75 ng/mL were associated with an increased risk of PSA recurrence within 2 years of radical prostatectomy.
Our study suggests that preoperative serum cell-free DNA concentration may be a useful prognostic biomarker for men with clinically localized prostate cancer treated with radical prostatectomy.
我们评估了接受根治性前列腺切除术的临床局限性前列腺癌男性患者术前血清游离循环DNA浓度与前列腺特异性抗原（PSA）复发之间的关联。
192例临床局限性前列腺癌男性患者构成了我们的研究人群，这些患者在约翰霍普金斯医院接受了根治性前列腺切除术，且有术前血清可供分析。所有血清样本均在前列腺活检前或前列腺活检后至少4个月采集。使用通过定量实时PCR生成的标准曲线计算每个样本中血清游离循环DNA的总量。PSA复发定义为术后单一PSA水平≥0.2。DNA浓度的自然对数（ln）用于统计分析。
在我们研究的192名男性中，56名（29%）在研究期间出现PSA复发（PSA复发的中位时间为2年）。最后一次随访时无疾病男性的中位随访时间为3年。研究中所有男性血清游离DNA浓度的中位数为5.3 ng/mL（平均18.05 ng/mL；范围0.2 - 320 ng/mL）。复发男性和未复发男性的平均血清DNA浓度分别为3.8±34.1和13.7±33.6 ng/mL（P = 0.001）。在单变量分析中，ln DNA浓度与PSA复发显著相关（风险比，1.49；95%置信区间，1.3 - 1.8；P < 0.001）。在多变量模型中，ln DNA浓度与PSA复发显著相关（风险比，2.56；95%置信区间，1.1 - 1.6；P = 0.003）。通过自助法分析，血清游离DNA浓度≥5.75 ng/mL与根治性前列腺切除术后2年内PSA复发风险增加相关。
我们的研究表明，术前血清游离DNA浓度可能是接受根治性前列腺切除术的临床局限性前列腺癌男性患者有用 的预后生物标志物。
