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摘要: 目的 通过前瞻性队列研究，探讨ETS相关基因(ETS-related gene，ERG)扩增水平作为前列腺癌根治术患者预后预测指标的价值。方法 通过荧光原位杂交的方法检测前列腺癌根治术患者组织样本中的ERG扩增水平，与患者的血清PSA水平、病理Gleason评分、病理分期、Ki-67表达水平进行相关性分析，并对患者的生化复发情况进行预测。结果 前瞻性队列共纳入152例接受前列腺癌根治术的患者，其中有53例的组织标本为ERG阳性(34.9%)。ERG扩增水平与病理Gleason评分(P < 0.05)和Ki-67表达水平(P < 0.05)显著相关。ERG阳性率在Gleason评分6分、7分和>7分组中分别为59%、39%和14%，而在Ki-67阳性比例 < 2%、2%~10%和＞10%组中分别为46%、26%和22%。此外，ERG扩增阳性在低血清PSA(P=0.256)和低病理T分期(P=0.200)的患者中更常见，但差异无统计学意义。Cox回归分析发现ERG阴性(HR=0.42，95%CI：0.17~1.03)和Ki-67高表达(HR=1.00，95%CI：0.96~1.02)均是前列腺癌根治术后患者生化复发的独立危险因素。根据Kaplan-Meier生存分析证实ERG阴性同时Ki-67高表达组的患者无生化复发生存时间最短，其次是ERG阴性同时Ki-67低表达组(P=0.058)和ERG阳性同时Ki-67低表达组(P < 0.01)，而ERG阳性同时Ki-67高表达组(P < 0.001)的无疾病进展生存时间最长。结论 在ERG整体阳性比例较低的人群中，ERG扩增水平是前列腺癌根治术后患者生化复发的独立预后因素。ERG与Ki-67等其他生物标志物的联合应用具有更理想的预测效能。Abstract: Objective To prospectively investigate the value of ETS-related gene(ERG) as a prognostic factor in patients undergoing radical prostatectomy.Methods The amplification level of ERG in tissue samples of patients undergoing radical prostatectomy was detected by fluorescence in situ hybridization. The correlation between ERG amplification level and serum PSA level, Gleason score, pathological stage and Ki-67 expression level were analyzed, and the predictive value for biochemical recurrence was estimated.Results A total of 152 patients who underwent radical prostatectomy were included, of which ERG was positive in 53 prostate cancer samples(34.9%). ERG was significantly associated with postoperative Gleason score(P < 0.05) and Ki-67 positive percentage(P < 0.05). The positive rate of ERG was significantly higher in patients with Gleason score=6(59%), compared with those having Gleason score=7(39%) or Gleason score>7(14%). The positive rate of ERG was significantly higher in patients with Ki-67 positive percentage < 2%(46%), compared with those having Ki-67 positive percentage 2%-10%(26%) and > 10%(22%). Furthermore, positive expression of ERG occurred more frequently in patients with lower PSA(P=0.256) and lower pathological T stage(P=0.200), but without statistically significant. Cox regression analysis showed that both ERG negative(HR=0.42, 95%CI: 0.17-1.03) and high Ki-67 expression(HR=1.00, 95%CI: 0.96-1.02) were independent risk factors for biochemical recurrence in patients after radical prostatectomy. Kaplan-Meier survival analysis confirmed that the subset of patients with negative ERG and high Ki-67 had the significant shorter biochemical recurrence-free survival compared to those with positive ERG and high Ki-67(P < 0.001) or those with positive ERG and low Ki-67(P < 0.01), while marginally shorter survival compared to those with negative ERG and low Ki-67(P=0.058).Conclusion Among the population with a low prevalence of ERG positive, ERG status is an independent prognostic factor for survival outcomes in patients undergoing radical prostatectomy. The combined application of ERG with other biomarkers such as Ki-67 might have better potential predictive value.
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Key words:
- prostate cancer /
- radical prostatectomy /
- ETS-related gene /
- biomarker /
- survival prognosis
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表 1 亚组分析中ERG扩增阳性患者所占比例的比较
例 临床病理特征 总病例数(152例) 病例数占比/% ERG扩增 阴性(99例) 阳性(53例) 阳性占比/% P值 PSA水平/(ng/mL) 0.26 < 10 43 28 25 18 42 ≥10 109 72 74 35 32 Gleason评分 6 17 11 7 10 59 < 0.05 7 98 65 60 38 39 > 7 37 24 32 5 14 病理T分期 0.20 T2a~b 24 16 13 11 46 T2c 76 50 47 29 38 T3a 30 20 21 9 30 T3b 22 14 18 4 18 Ki-67阳性比例/% < 0.05 < 2 72 47 39 33 46 2~10 53 35 39 14 26 ＞10 27 18 21 6 22 
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表 2 影响前列腺癌根治术后生化复发的危险因素Cox回归分析
临床病理特征 单因素Cox回归 多因素Cox回归 HR 95% CI P值 HR 95% CI P值 ERG扩增水平 0.22 0.09~0.52 < 0.001 0.42 0.17~1.03 < 0.05 年龄 1.00 0.96~1.04 0.913 PSA水平 3.62 1.29~10.16 < 0.010 Gleason评分 3.23 2.10~4.98 < 0.001 2.81 1.79~4.43 < 0.01 病理T分期 1.87 1.33~2.61 < 0.001 Ki-67蛋白水平 1.53 1.03~2.27 < 0.050 1.00 0.96~1.02 < 0.05
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