Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Gynecol Oncol. 2011 Jun 1;121(3):444-50. doi: 10.1016/j.ygyno.2011.01.025. Epub 2011 Feb 26.
MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression primarily through post-transcriptional modification. We tested the hypothesis that miRNA expression is associated with overall survival in advanced ovarian cancer.
Cases included newly diagnosed patients with stage III or IV serous ovarian cancer. RNA from a training set of 62 cases was hybridized to an miRNA microarray containing 470 mature human transcripts. Cox Regression was performed to identify miRNAs associated with overall survival. External validation was performed using quantitative RT-PCR miRNA assays in an independent test set of 123 samples. MiRNA targets and associated biologic pathways were predicted in silico.
Of all patients, 80% had high-grade, stage IIIC tumors and 64% underwent optimal cytoreduction. The median survival for the entire cohort was 49±4 months. The training set identified 3 miRNAs associated with survival--miR-337, miR-410, and miR-645. An miRNA signature containing miR-410 and miR-645 was most strongly associated with overall survival in the training set (HR=2.96, 95% CI: 1.51-5.78). This miRNA survival signature (MiSS) was validated in the test set (HR=1.71, 95% CI: 1.05-2.78). The MiSS was independent of FIGO stage and surgical debulking.
The data suggest that an MiSS that contains miR-410 and miR-645 is negatively associated with overall survival in advanced serous ovarian cancer. This signature, when further validated, may be useful in individualizing care for the ovarian cancer patient. Pathway analyses identify biologically plausible mechanisms.
微小 RNA（miRNA）是一类小的非编码 RNA，主要通过转录后修饰来负调控基因表达。我们检验了 miRNA 表达与晚期卵巢癌总生存期相关的假说。
纳入新诊断的 III 期或 IV 期浆液性卵巢癌患者。62 例患者的 RNA 与包含 470 个人成熟转录物的 miRNA 微阵列杂交。Cox 回归分析鉴定与总生存期相关的 miRNA。在包含 123 例样本的独立测试集中使用定量 RT-PCR miRNA 检测进行外部验证。通过计算机预测 miRNA 靶标和相关生物学途径。
所有患者中，80%为高级别、IIIIC 期肿瘤，64%进行了最佳肿瘤细胞减灭术。全队列的中位生存期为 49±4 个月。训练集确定了 3 个与生存相关的 miRNA——miR-337、miR-410 和 miR-645。包含 miR-410 和 miR-645 的 miRNA 特征在训练集中与总生存期的相关性最强（HR=2.96，95%CI：1.51-5.78）。该 miRNA 生存特征（MiSS）在测试集中得到验证（HR=1.71，95%CI：1.05-2.78）。MiSS 独立于 FIGO 分期和手术减瘤。
数据表明，包含 miR-410 和 miR-645 的 MiSS 与晚期浆液性卵巢癌的总生存期呈负相关。该特征如进一步验证，可能有助于对卵巢癌患者进行个体化治疗。通路分析确定了生物学上合理的机制。
