预测乳腺癌的生物标志物也可以用于预测膀胱癌患者的预后

  近日，一篇发表于国际杂志Molecular Cancer Research上的研究论文中，来自达特茅斯诺里斯癌症研究中心的研究人员利用大量的基因组数据研究发现，此前在乳腺癌中坚定的E2F4特性或许也可以用于预测膀胱癌患者对疗法的反应及预后表现。
  研究者Cheng说道，我们发现E2F4特性可以预测非肌肉侵入性和肌肉侵入性的膀胱癌，其同时还可以预测患者对膀胱内卡介苗疗法（BCG）的反应，而本文研究表明，正向E2F4分值的膀胱癌患者或可获益于BCG疗法，而负向E2F4分值的患者则和未进行治疗的癌症患者表现并无明显差异。
  膀胱内的BCG疗法曾经广泛被用于治疗浸润性的膀胱癌，而且有60%利用该疗法的患者都成功抑制了癌症的复发和进展，然而目前并没有有效的生物标志物来帮助鉴定哪些患者会对BCG疗法产生反应。而这项研究中，研究者发现生物标志物E2F4或可帮助预测非浸润性膀胱癌患者对BCG疗法的有效性反应，本文研究基于研究人员对超过800份膀胱癌样本的大量整合性分析而得出的。
  对大量基因组数据的整合或可帮助研究者深入地分析癌症的发展，同时也可以帮助鉴别出用于预测患者对癌症产生反应的有效生物标志物，本文研究中研究者进行了精细化的研究证实了生物标志物E2F4的预测价值，以此来进行膀胱癌发展以及患者复发情况的预测。后期研究者的目的是进行常规实际性的临床测试来检测BCG疗法对治疗膀胱癌的具体价值。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

E2F4 Program is Predictive of Progression and Intravesical Immunotherapy Efficacy in Bladder Cancer
Molecular Cancer Research     doi: 10.1158/1541-7786.MCR-15-0120
Chao Cheng1,*, Frederick S Varn2, and Carmen J Marsit3
Bladder cancer is a common malignant disease, with non-muscle-invasive bladder cancer (NMIBC) representing the majority of tumors. This cancer subtype is typically treated by transurethral resection. In spite of treatment, up to 70% of patients show local recurrences. Intravesical BCG (Bacillus Calmette-Guerin) immunotherapy has been widely used to treat NMIBC, but it fails to suppress recurrence of bladder tumors in up to 40% of patients. Therefore, the development of prognostic markers is needed to predict the progression of bladder cancer and the efficacy of intravesical BCG treatment. This study demonstrates the effectiveness of an E2F4 signature for prognostic prediction of bladder cancer. E2F4 scores for each sample in a bladder cancer expression dataset were calculated by summarizing the relative expression levels of E2F4 target genes identified by ChIP-seq, and then the scores were used to stratify patients into good and poor outcome groups. The molecular signature was investigated in a single bladder cancer dataset and then its effectiveness was confirmed in two meta-bladder datasets consisting of specimens from multiple independent studies. These results were consistent in different datasets and demonstrate that the E2F4 score is predictive of clinical outcomes in bladder cancer, with patients whose tumors exhibit an E2F4 score >0 having significantly shorter survival times than those with an E2F4 score <0, in both non-muscle invasive and muscle-invasive bladder cancer. Furthermore, although intravesical BCG immunotherapy can significantly improve the clinical outcome of NMIBC patients with positive E2F4 scores (E2F4>0 group), it does not show significant treatment effect for those with negative scores (E2F4<0 group). Implications: The E2F4 signature can be applied to predict the progression/recurrence, and the responsiveness of patients to intravesical BCG immunotherapy in bladder cancer.