Circulating tumor cell and cell-free RNA capture and expression analysis identify platelet-associated genes in metastatic lung cancer
Circulating tumor cell and cell-free RNA capture and expression analysis identify platelet-associated genes in metastatic lung cancer
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DOI：
10.1186/s12885-019-5795-x
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发表时间：
2019-06-19
期刊：
影响因子：
3.8
通讯作者：
Alpaugh, R. Katherine
中科院分区：
文献类型：
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作者：
Beck, Tim N.;Boumber, Yanis A.;Alpaugh, R. Katherine
背景循环肿瘤细胞（CTC）和血浆游离RNA（cfRNA）可作为肺癌预后和治疗反应的生物标志物。在精确肿瘤学中选择或常规使用CTC和血浆cfRNA的一个障碍是两者的量有限，并且CTC仅在转移性疾病中可见。由于CTC和血浆cfRNA的捕获提供了在没有侵入性程序的情况下监测和评估恶性肿瘤的机会，我们比较了CTC捕获和鉴定的两种方法，并分析了CTC和血浆cfRNA的mRNA以鉴定潜在的肿瘤相关生物标志物。两种方法用于CTC捕获：标准上皮细胞粘附分子（EpCam）CellSearch试剂盒（单捕获）和EpCAM加HER 2、EGFR和MUC-1特异性组合铁磁流体捕获（quadcapture）。对于quadcapture，另外使用抗细胞角蛋白7（CK 7）来辅助CTC鉴定。对血浆cfRNA和来自组合的铁磁流体分离的CTC的mRNA进行NanoString分析。使用STRING和Reactome.ResultsUnicapture检测CTC在40%的NSCLC和60%的小细胞肺癌的表达数据进行了分析，而quadcapture/CK 7确定CTC在20%的NSCLC和80%的小细胞肺癌。NanoString数据的生物信息学分析确定了血小板因子4（PF 4）相关组的transcripts.ConclusionsQuadcapture铁磁流体试剂的高表达并没有显着提高CTC捕获效率。基于CTC和血浆cfRNA数据的NanoString分析强调了转移性肺癌患者中有趣的PF-4中心网络。
BackgroundCirculating tumor cells (CTC) and plasma cell-free RNA (cfRNA) can serve as biomarkers for prognosis and treatment response in lung cancer. One barrier to the selected or routine use of CTCs and plasma cfRNA in precision oncology is the limited quantity of both, and CTCs are only seen in metastatic disease. As capture of CTCs and plasma cfRNA presents an opportunity to monitor and assess malignancies without invasive procedures, we compared two methods for CTC capture and identification, and profiled mRNA from CTCs and plasma cfRNA to identify potential tumor-associated biomarkers.MethodsPeripheral blood was collected from ten patients with small cell lung cancer (SCLC), ten patients with non-small cell lung cancer (NSCLC) and four healthy volunteers. Two methods were used for CTC capture: the standard epithelial cell adhesion molecule (EpCam) CellSearch kit (unicapture) and EpCAM plus HER2, EGFR and MUC-1 specific combined ferrofluid capture (quadcapture). For the quadcapture, anti-cytokeratin 7 (CK7) was additionally used to assist in CTC identification. NanoString analysis was performed on plasma cfRNA and on mRNA from combined ferrofluid isolated CTCs. Expression data was analyzed using STRING and Reactome.ResultsUnicapture detected CTCs in 40% of NSCLC and 60% of SCLC; whereas, quadcapture/CK7 identified CTCs in 20% of NSCLC and 80% of SCLC. Bioinformatic analysis of NanoString data identified high expression of a platelet factor 4 (PF4)-related group of transcripts.ConclusionsQuadcapture ferrofluid reagent did not significantly improve CTC capture efficacy. NanoString analysis based on CTC and plasma cfRNA data highlighted an intriguing PF-4-centric network in patients with metastatic lung cancer.