基于循环肿瘤细胞和上皮-间充质转化的上皮性卵巢癌复发预后列线图的建立与验证。

We aimed to determine the prognosis value of circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition in epithelial ovarian cancer (EOC) recurrence. We used CanPatrol CTC-enrichment technique to detect CTCs from blood samples and classify subpopulations into epithelial, mesenchymal, and hybrids. To construct nomogram, prognostic factors were selected by Cox regression analysis. Risk stratification was performed through Kaplan-Meier analysis among the training group (n = 114) and validation group (n = 38). By regression screening, both CTC counts (HR 1.187; 95% CI 1.098-1.752; p = 0.012) and M-CTC (HR 1.098; 95% CI 1.047-1.320; p = 0.009) were demonstrated as independent factors for recurrence. Other variables including pathological grade, FIGO stage, lymph node metastasis, ascites, and CA-125 were also selected (p < 0.005) to construct nomogram. The C-index of internal and external validation for nomogram was 0.913 and 0.874. We found significant predictive values for the nomogram with/without CTCs (AUC 0.8705 and 0.8097). Taking CTC counts and M-CTC into separation, the values were 0.8075 and 0.8262. Finally, survival curves of risk stratification based on CTC counts (p = 0.0241), M-CTC (p = 0.0107), and the nomogram (p = 0.0021) were drawn with significant differences. In conclusion, CTCs could serve as a novel factor for EOC prognosis. Nomogram model constructed by CTCs and other clinical parameters could predict EOC recurrence and perform risk stratification for clinical decision-making.Trial registration Chinese Clinical Trial Registry, ChiCTR-DDD-16009601, October 25, 2016.

我们旨在确定经历上皮-间充质转化的循环肿瘤细胞（CTC）在卵巢上皮癌（EOC）复发中的预后价值。我们使用 CanPatrol CTC 富集技术从血液样本中检测 CTC 并将亚群分类为上皮、间充质和混合。为了构建列线图，通过 Cox 回归分析选择预后因素。在训练组（n=114）和验证组（n=38）中通过 Kaplan-Meier 分析进行风险分层。通过回归筛选，CTC 计数（HR 1.187；95%CI 1.098-1.752；p=0.012）和 M-CTC（HR 1.098；95%CI 1.047-1.320；p=0.009）均被证明是复发的独立因素。其他变量，包括病理分级、FIGO 分期、淋巴结转移、腹水和 CA-125，也被选择（p<0.005）来构建列线图。内部和外部验证的列线图 C 指数分别为 0.913 和 0.874。我们发现列线图有显著的预测值，无论是否有 CTC（AUC 0.8705 和 0.8097）。将 CTC 计数和 M-CTC 分开，值分别为 0.8075 和 0.8262。最后，根据 CTC 计数（p=0.0241）、M-CTC（p=0.0107）和列线图（p=0.0021）绘制的风险分层生存曲线有显著差异。总之，CTC 可作为 EOC 预后的新因素。由 CTC 和其他临床参数构建的列线图模型可预测 EOC 复发并进行临床决策的风险分层。

试验注册：中国临床试验注册中心，ChiCTR-DDD-16009601，2016 年 10 月 25 日。