Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA 30322, USA.
Am J Pathol. 2011 Jul;179(1):46-54. doi: 10.1016/j.ajpath.2011.03.008. Epub 2011 May 3.
An important challenge in prostate cancer research is to develop effective predictors of tumor recurrence following surgery to determine whether immediate adjuvant therapy is warranted. To identify biomarkers predictive of biochemical recurrence, we isolated the RNA from 70 formalin-fixed, paraffin-embedded radical prostatectomy specimens with known long-term outcomes to perform DASL expression profiling with a custom panel that we designed of 522 prostate cancer-relevant genes. We identified a panel of 10 protein-coding genes and two miRNA genes (RAD23B, FBP1, TNFRSF1A, CCNG2, NOTCH3, ETV1, BID, SIM2, LETMD1, ANXA1, miR-519d, and miR-647) that could be used to separate patients with and without biochemical recurrence (P < 0.001), as well as for the subset of 42 Gleason score 7 patients (P < 0.001). We performed an independent validation analysis on 40 samples and found that the biomarker panel was also significant at prediction of biochemical recurrence for all cases (P = 0.013) and for a subset of 19 Gleason score 7 cases (P = 0.010), both of which were adjusted for relevant clinical information including T-stage, prostate-specific antigen, and Gleason score. Importantly, these biomarkers could significantly predict clinical recurrence for Gleason score 7 patients. These biomarkers may increase the accuracy of prognostication following radical prostatectomy using formalin-fixed specimens.
前列腺癌研究中的一个重要挑战是开发有效的肿瘤复发预测因子，以确定是否需要立即进行辅助治疗。为了确定预测生化复发的生物标志物，我们从 70 例福尔马林固定、石蜡包埋的根治性前列腺切除术标本中分离出 RNA，这些标本具有已知的长期结果，并使用我们设计的包含 522 个前列腺癌相关基因的定制 DASL 表达谱进行分析。我们确定了一个由 10 个蛋白编码基因和 2 个 miRNA 基因（RAD23B、FBP1、TNFRSF1A、CCNG2、NOTCH3、ETV1、BID、SIM2、LETMD1、ANXA1、miR-519d 和 miR-647）组成的基因表达谱，可用于区分有和无生化复发的患者（P<0.001），以及亚组的 42 例 Gleason 评分 7 患者（P<0.001）。我们对 40 例样本进行了独立验证分析，发现该生物标志物谱在所有病例（P=0.013）和亚组的 19 例 Gleason 评分 7 病例（P=0.010）的生化复发预测中也具有显著意义，这两个亚组均根据包括 T 分期、前列腺特异性抗原和 Gleason 评分在内的相关临床信息进行了调整。重要的是，这些生物标志物可以显著预测 Gleason 评分 7 患者的临床复发。这些生物标志物可能会提高使用福尔马林固定标本进行根治性前列腺切除术后的预后准确性。
