Halvorsen Ann Rita, Kristensen Gunnar, Embleton Andy, Adusei Cybil, Barretina-Ginesta Maria Pilar, Beale Philip, Helland Åslaug
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
Department of Gynecologic Oncology, Institute for Cancer Genetics and Informatics and University of Oslo, Oslo, Norway.
Dis Markers. 2017;2017:3098542. doi: 10.1155/2017/3098542. Epub 2017 Feb 15.
Ovarian cancer patients are recognized with poor prognosis. This study aimed to identify microRNAs in plasma for predicting response to treatment and outcome. We have investigated microRNAs in plasma from ovarian cancer patients enrolled in a large multicenter study (ICON7), investigating the effect of adding bevacizumab to standard chemotherapy in patients diagnosed with epithelial ovarian cancer. Patients with different histology, grade, and FIGO stages were included ( = 207) in this study. Screening of 754 unique microRNAs was performed in the discovery phase ( = 91) using TaqMan Low Density Arrays. The results were validated using single assays and RT-qPCR. Low levels of miR-200b, miR-1274A (tRNA), and miR-141 were significantly associated with better survival, confirmed with log-rank test in the validation set. The level of miR-1274A (tRNA) correlated with outcome was especially pronounced in the high-grade serous tumors. Interestingly, low level of miR-200c was associated with 5-month prolongation of PFS when treated with bevacizumab compared to standard chemotherapy. We found prognostic significance of miR-200b, miR-141, and miR-1274A (tRNA) in all histological types, where miR-1274A (tRNA) may be a specific marker in high-grade serous tumors. The level of miR-200c may be predictive of effect of treatment with bevacizumab. However, this needs further validation.
卵巢癌患者的预后较差。本研究旨在鉴定血浆中的微小RNA，以预测治疗反应和预后。我们对参与一项大型多中心研究（ICON7）的卵巢癌患者血浆中的微小RNA进行了研究，该研究调查了在确诊为上皮性卵巢癌的患者中，在标准化疗基础上加用贝伐单抗的效果。本研究纳入了不同组织学类型、分级和国际妇产科联盟（FIGO）分期的患者（n = 207）。在发现阶段（n = 91），使用TaqMan低密度阵列对754种独特的微小RNA进行了筛选。结果通过单检测法和逆转录定量聚合酶链反应（RT-qPCR）进行了验证。低水平的miR-200b、miR-1274A（tRNA）和miR-141与较好的生存率显著相关，在验证集中通过对数秩检验得到证实。miR-1274A（tRNA）与预后的相关性在高级别浆液性肿瘤中尤为明显。有趣的是，与标准化疗相比，用贝伐单抗治疗时，低水平的miR-200c与无进展生存期延长5个月相关。我们发现miR-200b、miR-141和miR-1274A（tRNA）在所有组织学类型中均具有预后意义，其中miR-1274A（tRNA）可能是高级别浆液性肿瘤的特异性标志物。miR-200c的水平可能预测贝伐单抗治疗的效果。然而，这需要进一步验证。
