标题： 卵巢癌贝伐珠单抗反应者的转录组特征 显示英文标题

标题： Transcriptome signature for the identification of bevacizumab responders in ovarian cancer

摘要： 卵巢癌的标准治疗包括减瘤手术，随后进行辅助铂类化疗联合紫杉醇治疗，并使用抗血管生成化合物贝伐珠单抗和/或PARP抑制剂进行维持治疗。 然而，目前尚无明确的临床指征说明贝伐珠单抗的使用，这突显了评估贝伐珠单抗反应的生物标志物的迫切需求。 在本研究中，基于一个新颖的RNA-seq数据集（n=181）和一个之前发表的微阵列数据集（n=377），我们已经鉴定出一个可能与贝伐珠单抗添加获益相关的表达特征，该特征被认为反映了由CTCFL激活驱动的癌症干细胞获得。 在新颖队列（HR=0.41(0.23-0.74)，adj.p-value=7.70e-03）和之前发表的队列（HR=0.51(0.34-0.75)，adj.p-value=3.25e-03）中，具有该特征的患者在接受标准化疗时加入贝伐珠单抗后表现出总体生存率的改善，而在对该特征呈阴性的患者中未观察到由治疗解释的生存差异。 除了CTCFL特征外，我们还发现了一些其他可重复的表达特征，这些特征可能代表与已知卵巢癌分子亚型无关的生物标志物候选者，需要基于更多RNA-seq数据的进一步验证研究。 显示英文摘要

摘要： The standard of care for ovarian cancer comprises cytoreductive surgery, followed by adjuvant platinum-based chemotherapy plus taxane therapy and maintenance therapy with the antiangiogenic compound bevacizumab and/or a PARP inhibitor. Nevertheless, there is currently no clear clinical indication for the use of bevacizumab, highlighting the urgent need for biomarkers to assess the response to bevacizumab. In the present study, based on a novel RNA-seq dataset (n=181) and a previously published microarray-based dataset (n=377), we have identified an expression signature potentially associated with benefit from bevacizumab addition and assumed to reflect cancer stemness acquisition driven by activation of CTCFL. Patients with this signature demonstrated improved overall survival when bevacizumab was added to standard chemotherapy in both novel (HR=0.41(0.23-0.74), adj.p-value=7.70e-03) and previously published cohorts (HR=0.51(0.34-0.75), adj.p-value=3.25e-03), while no significant differences in survival explained by treatment were observed in patients negative for this signature. In addition to the CTCFL signature, we found several other reproducible expression signatures which may also represent biomarker candidates not related to established molecular subtypes of ovarian cancer and require further validation studies based on additional RNA-seq data.