Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Clin Cancer Res. 2017 Sep 1;23(17):5112-5122. doi: 10.1158/1078-0432.CCR-16-3081. Epub 2017 Jun 14.
To develop an approach for the investigation of different subtypes of circulating tumor cells (CTC) and other cells to evaluate their potential prognostic value of prostate cancer. Malignancy of CTCs undergoing epithelial-to-mesenchymal transition (EMT) was confirmed by repeated FISH. Subgroups of CTCs in 81 patients with prostate cancer (43 castration resistant and 38 untreated localized) were correlated to disease aggressiveness parameters. AUC analysis was applied to compare the performance for metastasis prediction between serum PSA level alone and a combined risk score using both PSA and EMTing CTC count. Circulating megakaryocytes and cancer patient survival association was performed using Cox model. The majority of vimentin (VIM)/CD45 cells were malignant, with genomic alterations in several genomic regions. The number of cytokeratin (CK)/VIM/CD45 CTCs correlated with disease burden, tumor aggressiveness, and poorer survival. Meanwhile, CK/VIM/CD45 CTCs were associated with metastases better than other subtypes of CTCs in these limited samples. Combination of PSA level and the number of CK/VIM/CD45 CTCs enhanced the prediction of cancer metastases [AUC, 0.921; 95% confidence interval (CI), 0.858-0.985]. The number of circulating megakaryocytes was potentially associated with good patient survival in advanced prostate cancer (HR, 0.849; 95% CI, 0.628-1.146, per cell increase), and the difference between the number of mesenchymal CTCs and megakaryocytes strongly correlated to poor survival (HR, 10.17; 95% CI, 2.164-47.789, if score ≥2.0). This CTC analysis approach and the potential association of megakaryocytes with cancer prognosis may greatly enhance our ability to investigate the cancer metastasis process and to predict/monitor cancer progression. .
为了研究不同类型的循环肿瘤细胞（CTC）和其他细胞，以评估其在前列腺癌中的潜在预后价值，我们开发了一种方法。通过反复进行荧光原位杂交（FISH）证实了经历上皮间质转化（EMT）的 CTC 的恶性程度。将 81 例前列腺癌患者（43 例去势抵抗，38 例局部未治疗）的 CTC 亚群与疾病侵袭性参数相关联。应用 AUC 分析比较单独血清 PSA 水平和使用 PSA 和 EMTingCTC 计数的联合风险评分在预测转移方面的性能。使用 Cox 模型分析循环巨核细胞与癌症患者生存的相关性。大多数波形蛋白（VIM）/CD45 细胞是恶性的，在几个基因组区域存在基因组改变。细胞角蛋白（CK）/VIM/CD45 CTC 的数量与疾病负担、肿瘤侵袭性和较差的生存相关。同时，在这些有限的样本中，CK/VIM/CD45 CTC 与转移的相关性优于其他 CTC 亚型。PSA 水平和 CK/VIM/CD45 CTC 数量的组合增强了对癌症转移的预测[AUC，0.921；95%置信区间（CI），0.858-0.985]。循环巨核细胞的数量与晚期前列腺癌患者的良好生存相关（HR，0.849；95%CI，0.628-1.146，每增加一个细胞），并且间充质 CTC 数量与巨核细胞之间的差异与不良生存密切相关（HR，10.17；95%CI，2.164-47.789，如果评分≥2.0）。这种 CTC 分析方法和巨核细胞与癌症预后的潜在关联可能极大地增强我们研究癌症转移过程和预测/监测癌症进展的能力。
