Sun Na, Lee Yi-Te, Kim Minhyung, Wang Jasmine J, Zhang Ceng, Teng Pai-Chi, Qi Dongping, Zhang Ryan Y, Tran Benjamin V, Lee Yue Tung, Ye Jinglei, Palomique Juvelyn, Nissen Nicholas N, Han Steven-Huy B, Sadeghi Saeed, Finn Richard S, Saab Sammy, Busuttil Ronald W, Posadas Edwin M, Liang Li, Pei Renjun, Yang Ju Dong, You Sungyong, Agopian Vatche G, Tseng Hsian-Rong, Zhu Yazhen
California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles (UCLA), 570 Westwood Plaza, Los Angeles, CA 90095, USA.
Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Adv Mater Technol. 2021 May;6(5). doi: 10.1002/admt.202001056. Epub 2021 Apr 9.
Transcriptomic profiling of tumor tissues introduces a large database, which has led to improvements in the ability of cancer diagnosis, treatment, and prevention. However, performing tumor transcriptomic profiling in the clinical setting is very challenging since the procurement of tumor tissues is inherently limited by invasive sampling procedures. Here, we demonstrated the feasibility of purifying hepatocellular carcinoma (HCC) circulating tumor cells (CTCs) from clinical patient samples with improved molecular integrity using Click Chips in conjunction with a multimarker antibody cocktail. The purified CTCs were then subjected to mRNA profiling by NanoString nCounter platform, targeting 64 HCC-specific genes, which were generated from an integrated data analysis framework with 8 tissue-based prognostic gene signatures from 7 publicly available HCC transcriptomic studies. After bioinformatics analysis and comparison, the HCC CTC-derived gene signatures showed high concordance with HCC tissue-derived gene signatures from TCGA database, suggesting that HCC CTCs purified by Click Chips could enable the translation of HCC tissue molecular profiling into a noninvasive setting.
肿瘤组织的转录组分析引入了一个庞大的数据库，这使得癌症诊断、治疗和预防能力得到了提高。然而，在临床环境中进行肿瘤转录组分析极具挑战性，因为肿瘤组织的获取本质上受到侵入性采样程序的限制。在这里，我们证明了使用Click Chips结合多标记抗体混合物从临床患者样本中纯化具有改善的分子完整性的肝细胞癌（HCC）循环肿瘤细胞（CTC）的可行性。然后，通过NanoString nCounter平台对纯化的CTC进行mRNA分析，靶向64个HCC特异性基因，这些基因来自一个综合数据分析框架，该框架整合了来自7项公开可用的HCC转录组研究的8个基于组织的预后基因特征。经过生物信息学分析和比较，HCC CTC衍生的基因特征与来自TCGA数据库的HCC组织衍生的基因特征高度一致，这表明通过Click Chips纯化的HCC CTC能够将HCC组织分子分析转化为非侵入性环境。
