Department of Urology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
Eur Urol. 2010 Jan;57(1):12-20. doi: 10.1016/j.eururo.2009.09.013. Epub 2009 Sep 9.
Currently, tumor grade is the best predictor of outcome at first presentation of noninvasive papillary (Ta) bladder cancer. However, reliable predictors of Ta tumor recurrence and progression for individual patients, which could optimize treatment and follow-up schedules based on specific tumor biology, are yet to be identified.
To identify genes predictive for recurrence and progression in Ta bladder cancer at first presentation using a quantitative, pathway-specific approach.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of patients with Ta G2/3 bladder tumors at initial presentation with three distinct clinical outcomes: absence of recurrence (n=16), recurrence without progression (n=16), and progression to carcinoma in situ or invasive disease (n=16).
Expressions of 24 genes that feature in relevant pathways that are deregulated in bladder cancer were quantified by real-time polymerase chain reaction on tumor biopsies from the patients at initial presentation.
CCND3 (p=0.003) and HRAS (p=0.01) were predictive for recurrence by univariate analysis. In a multivariable model based on CCND3 expression, sensitivity and specificity for recurrence were 97% and 63%, respectively. HRAS (p<0.001), E2F1 (p=0.017), BIRC5/Survivin (p=0.038), and VEGFR2 (p=0.047) were predictive for progression by univariate analysis. Multivariable analysis based on HRAS, VEGFR2, and VEGF identified progression with 81% sensitivity and 94% specificity. Since this is a small retrospective study using medium-throughput profiling, larger confirmatory studies are needed.
Gene expression profiling across relevant cancer pathways appears to be a promising approach for Ta bladder tumor outcome prediction at initial diagnosis. These results could help differentiate between patients who need aggressive versus expectant management.
目前，肿瘤分级是预测非浸润性乳头状（Ta）膀胱癌初次就诊时结局的最佳指标。然而，仍需要确定能够预测 Ta 膀胱癌肿瘤复发和进展的可靠指标，以便根据特定的肿瘤生物学特征优化治疗和随访方案。
采用定量、通路特异性方法，鉴定初诊 Ta 膀胱癌肿瘤复发和进展的预测基因。
设计、地点和参与者：回顾性研究初诊时患有 TaG2/3 膀胱癌且具有 3 种不同临床结局的患者：无复发（n=16）、复发但无进展（n=16）和进展为原位癌或浸润性疾病（n=16）。
应用实时聚合酶链反应对患者肿瘤活检组织中涉及膀胱癌中失调通路的 24 个基因的表达进行定量分析。
单变量分析显示，CCND3（p=0.003）和 HRAS（p=0.01）可预测复发。基于 CCND3 表达的多变量模型中，复发的敏感性和特异性分别为 97%和 63%。单变量分析显示，HRAS（p<0.001）、E2F1（p=0.017）、BIRC5/Survivin（p=0.038）和 VEGFR2（p=0.047）可预测进展。基于 HRAS、VEGFR2 和 VEGF 的多变量分析可识别出具有 81%敏感性和 94%特异性的进展。由于这是一项使用中通量分析的小回顾性研究，因此需要更大的验证性研究。
跨相关癌症通路的基因表达谱分析似乎是一种很有前途的 Ta 膀胱癌初诊时预测肿瘤结局的方法。这些结果有助于区分需要积极治疗和期待治疗的患者。
