Witek Małgorzata A, Aufforth Rachel D, Wang Hong, Kamande Joyce W, Jackson Joshua M, Pullagurla Swathi R, Hupert Mateusz L, Usary Jerry, Wysham Weiya Z, Hilliard Dawud, Montgomery Stephanie, Bae-Jump Victoria, Carey Lisa A, Gehrig Paola A, Milowsky Matthew I, Perou Charles M, Soper John T, Whang Young E, Yeh Jen Jen, Martin George, Soper Steven A
Department of Chemistry, The University of Kansas, Lawrence, KS 66047, USA.
Center of Biomodular Multiscale Systems for Precision Medicine, The University of Kansas, Lawrence, KS 66047, USA.
NPJ Precis Oncol. 2017;1. doi: 10.1038/s41698-017-0028-8. Epub 2017 Jul 25.
Circulating tumor cells consist of phenotypically distinct subpopulations that originate from the tumor microenvironment. We report a circulating tumor cell dual selection assay that uses discrete microfluidics to select circulating tumor cell subpopulations from a single blood sample; circulating tumor cells expressing the established marker epithelial cell adhesion molecule and a new marker, fibroblast activation protein alpha, were evaluated. Both circulating tumor cell subpopulations were detected in metastatic ovarian, colorectal, prostate, breast, and pancreatic cancer patients and 90% of the isolated circulating tumor cells did not co-express both antigens. Clinical sensitivities of 100% showed substantial improvement compared to epithelial cell adhesion molecule selection alone. Owing to high purity (>80%) of the selected circulating tumor cells, molecular analysis of both circulating tumor cell subpopulations was carried out in bulk, including next generation sequencing, mutation analysis, and gene expression. Results suggested fibroblast activation protein alpha and epithelial cell adhesion molecule circulating tumor cells are distinct subpopulations and the use of these in concert can provide information needed to navigate through cancer disease management challenges.
循环肿瘤细胞由源自肿瘤微环境的表型不同的亚群组成。我们报告了一种循环肿瘤细胞双重选择检测方法，该方法使用离散微流控技术从单个血样中选择循环肿瘤细胞亚群；对表达既定标志物上皮细胞粘附分子和新标志物成纤维细胞活化蛋白α的循环肿瘤细胞进行了评估。在转移性卵巢癌、结直肠癌、前列腺癌、乳腺癌和胰腺癌患者中均检测到了这两种循环肿瘤细胞亚群，且90%的分离循环肿瘤细胞不共表达这两种抗原。与单独选择上皮细胞粘附分子相比，临床敏感性达100%，有显著提高。由于所选循环肿瘤细胞的纯度较高（>80%），对这两种循环肿瘤细胞亚群进行了批量分子分析，包括下一代测序、突变分析和基因表达分析。结果表明，成纤维细胞活化蛋白α和上皮细胞粘附分子循环肿瘤细胞是不同的亚群，联合使用这些细胞可以提供应对癌症疾病管理挑战所需的信息。
