A 20-gene model for molecular nodal staging of bladder cancer: development and prospective assessment.
A 20-gene model for molecular nodal staging of bladder cancer: development and prospective assessment.
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DOI：
10.1016/s1470-2045(10)70296-5
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发表时间：
2011-02
期刊：
影响因子：
51.1
通讯作者：
Theodorescu, Dan
中科院分区：
文献类型：
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作者：
Smith, Steven Christopher;Baras, Alexander Spyridon;Dancik, Garrett;Ru, Yuanbin;Ding, Kuan-Fu;Moskaluk, Christopher A.;Fradet, Yves;Lehmann, Jan;Stoeckle, Michael;Hartmann, Arndt;Lee, Jae K.;Theodorescu, Dan
膀胱癌术前新辅助化疗可提高生存率。然而，它还没有被广泛采用，因为大多数患者没有受益，我们目前无法预测那些受益的患者。由于膀胱癌术后复发的最重要预测因素是病理阳性淋巴结，我们建议定义该阶段的工具在选择新辅助化疗患者时是有用的。我们开发了一种预测病理性淋巴结状态的基因表达模型（GEM），用于临床淋巴结阴性（cN 0）患者的原发性肿瘤组织。从成对冷冻和福尔马林固定组织（N=32对）的微阵列忠实地检测到的转录物的子集，我们开发了GEM和截止值，其使用两个单独的训练队列（N=90和N=66）鉴定具有升高的淋巴结受累风险的患者分层。然后，我们评估了GEM和截止值，以预测来自III期试验队列（AUO-AB-05/95，N=185）的组织中的淋巴结阳性疾病。开发了20个基因的GEM，并显示AUC= 0.67 [95%CI 0.59 - 0.75]，用于在AUO-AB-05/95中预测cyber 2时的淋巴结疾病。截止系统确定了淋巴结阳性疾病相对风险高（RR 1.74，[1.03 - 2.93]）和低（RR 0.70，[0.51 - 0.96]）的受试者。多因素Logistic回归分析显示，GEM预测因子与年龄、性别、病理分期和淋巴管浸润无关（P= 0.019）。根据淋巴结阳性疾病的风险选择新辅助化疗的患者有可能使高危患者受益，同时避免其他毒性和延迟化疗。美国国家癌症研究所（R 01 CA 143971）
Neoadjuvant chemotherapy prior to cystectomy confers a survival benefit in bladder cancer. Yet, it has not been widely adopted, since most patients do not benefit and we are currently unable to predict those that do. As the most important predictor of recurrence following cystectomy is pathologically positive nodes, we propose that tools defining this stage would be useful in selecting patients for neoadjuvant chemotherapy. We developed a gene expression model (GEM) predictive of pathological node status for use on primary tumor tissue from clinically node negative (cN0) patients. From a subset of transcripts detected faithfully by microarrays from both paired frozen and formalin fixed tissues (N=32 pairs), we developed both the GEM and cutoffs identifying patient strata with elevated risk of nodal involvement using two separate training cohorts (N=90 and N=66). We then evaluated the GEM and cutoffs to predict node positive disease in tissues from a Phase III trial cohort (AUO-AB-05/95, N=185). A 20-gene GEM was developed and exhibited an AUC=0·67 [95%CI 0·59–0·75], for prediction of nodal disease at cystectomy in AUO-AB-05/95. The cutoff system identified subjects with high (RR 1·74, [1·03–2·93]) and low (RR 0·70, [0·51–0·96]) relative risk of node positive disease. Multivariate logistic regression demonstrated the GEM predictor was independent of age, gender, pathologic stage, and lymphovascular space invasion (P=0·019). Selecting patients for neoadjuvant chemotherapy based on risk of node positive disease has the potential to benefit high-risk patients while sparing others toxicity and delay to cystectomy. U.S. National Cancer Institute (R01CA143971)