Chen Jie-Fu, Ho Hao, Lichterman Jake, Lu Yi-Tsung, Zhang Yang, Garcia Mitch A, Chen Shang-Fu, Liang An-Jou, Hodara Elisabeth, Zhau Haiyen E, Hou Shuang, Ahmed Rafi S, Luthringer Daniel J, Huang Jiaoti, Li Ker-Chau, Chung Leland W K, Ke Zunfu, Tseng Hsian-Rong, Posadas Edwin M
Urologic Oncology Program and Uro-Oncology Research Laboratories, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Department of Statistics, University of California at Los Angeles, Los Angeles, California.
Cancer. 2015 Sep 15;121(18):3240-51. doi: 10.1002/cncr.29455. Epub 2015 May 14.
Although enumeration of circulating tumor cells (CTCs) has shown some clinical value, the pool of CTCs contains a mixture of cells that contains additional information that can be extracted. The authors subclassified CTCs by shape features focusing on nuclear size and related this with clinical information.
A total of 148 blood samples were obtained from 57 patients with prostate cancer across the spectrum of metastatic states: no metastasis, nonvisceral metastasis, and visceral metastasis. CTCs captured and enumerated on NanoVelcro Chips (CytoLumina, Los Angeles, Calif) were subjected to pathologic review including nuclear size. The distribution of nuclear size was analyzed using a Gaussian mixture model. Correlations were made between CTC subpopulations and metastatic status.
Statistical modeling of nuclear size distribution revealed 3 distinct subpopulations: large nuclear CTCs, small nuclear CTCs, and very small nuclear CTCs (vsnCTCs). Small nuclear CTCs and vsnCTC identified those patients with metastatic disease. However, vsnCTC counts alone were found to be elevated in patients with visceral metastases when compared with those without (0.36 ± 0.69 vs 1.95 ± 3.77 cells/mL blood; P<.001). Serial enumeration studies suggested the emergence of vsnCTCs occurred before the detection of visceral metastases.
There are morphologic subsets of CTCs that can be identified by fundamental pathologic approaches, such as nuclear size measurement. The results of this observational study strongly suggest that CTCs contain relevant information regarding disease status. In particular, the detection of vsnCTCs was found to be correlated with the presence of visceral metastases and should be formally explored as a putative blood-borne biomarker to identify patients at risk of developing this clinical evolution of prostate cancer.
尽管循环肿瘤细胞（CTC）计数已显示出一定的临床价值，但CTC池中包含的细胞混合物含有可提取的额外信息。作者通过关注核大小的形状特征对CTC进行亚分类，并将其与临床信息相关联。
从57例处于不同转移状态的前列腺癌患者中获取了148份血样，这些转移状态包括：无转移、非内脏转移和内脏转移。在纳米维可牢芯片（CytoLumina，加利福尼亚州洛杉矶）上捕获并计数的CTC接受了包括核大小在内的病理检查。使用高斯混合模型分析核大小的分布。对CTC亚群与转移状态之间进行相关性分析。
核大小分布的统计模型揭示了3个不同的亚群：大核CTC、小核CTC和极小核CTC（vsnCTC）。小核CTC和vsnCTC可识别出患有转移性疾病的患者。然而，与无内脏转移的患者相比，内脏转移患者的vsnCTC计数单独升高（0.36±0.69个细胞/毫升血液对1.95±3.77个细胞/毫升血液；P<0.001）。系列计数研究表明，vsnCTC的出现发生在内脏转移检测之前。
可以通过基本的病理方法，如核大小测量，识别出CTC的形态学亚群。这项观察性研究的结果强烈表明，CTC包含有关疾病状态的相关信息。特别是，发现vsnCTC的检测与内脏转移的存在相关，应将其作为一种假定的血源性生物标志物进行正式研究，以识别有发生前列腺癌这种临床进展风险的患者。
