Three-dimensional nanostructured substrates enable dynamic detection of ALK-rearrangement in circulating tumor cells from treatment-naive patients with stage III/IV lung adenocarcinoma.
Three-dimensional nanostructured substrates enable dynamic detection of ALK-rearrangement in circulating tumor cells from treatment-naive patients with stage III/IV lung adenocarcinoma.
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三维纳米结构基质能够动态检测未经治疗的 III/IV 期肺腺癌患者循环肿瘤细胞中的 ALK 重排
DOI：
10.1186/s12967-019-1779-5
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发表时间：
2019
影响因子：
7.4
通讯作者：
Zunfu Ke
中科院分区：
文献类型：
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作者：
Weiling He;Di Xu;Zhuo Wang;Hui Wu;Xianhong Xiang;Bing Tang;Wenting Jiang;Yongmei Cui;Han Wang;Neng Jiang;Yu Sun;Yangshan Chen;Shuhua Li;Minzhi Hou;Yang Zhang;Liantang Wang;Zunfu Ke
研究背景循环肿瘤细胞（CTC）在实现癌症患者精准医疗方面具有巨大的前景。在III或IV期肺腺癌中测试NanoVelcro CTC捕获效率。此外，ALK-重排状态进行了检查，通过荧光原位杂交在CTC富集NanoVelcro.ResultsNanoVelcro系统显示出更高的CTC捕获效率比CellSearch在III或IV期肺腺癌。两种方法测得的CTC计数呈正相关（r = 0.45，p < 0.05）。此外，通过NanoVelcro确定的CTC计数和pTNM分期之间的相关性比通过CellSearch确定的更显著（p < 0.001 VS p = 0.029）。所有ALK阳性患者每ml血液中有3个或更多ALK重排CTC。在ALK阴性患者中检测到少于3个ALK重排CTC。NanoVelcro可检测ALK重排状态，与活检检测相比具有一致的灵敏度和特异性。此外，ALK重排的CTC比率与ALK阳性患者的pTNM分期相关。随访结果显示，NanoVelcro计数CTC在评价氯唑替尼的短期和长期疗效方面均比CellSearch更稳定可靠。NanoVelcro CTC计数的变化可准确反映疾病进展。结论NanoVelcro为晚期NSCLC CTC计数和定性提供了一种敏感的方法。NanoVelcro可检测到晚期NSCLC患者CTC中的ALK重排，有助于诊断测试和预后分析，最重要的是提供了一种实时监测治疗反应的无创方法。
BackgroundCirculating tumor cells (CTC) shows great prospect to realize precision medicine in cancer patients.MethodsWe developed the NanoVelcro Chip integrating three functional mechanisms. NanoVelcro CTC capture efficiency was tested in stage III or IV lung adenocarcinoma. Further, ALK-rearrangement status was examined through fluorescent in situ hybridization in CTCs enriched by NanoVelcro.ResultsNanoVelcro system showed higher CTC-capture efficiency than CellSearch in stage III or IV lung adenocarcinoma. CTC counts obtained by both methods were positively correlated (r = 0.45, p < 0.05). Further, Correlation between CTC counts and pTNM stage determined by NanoVelcro was more significant than that determined by CellSearch (p < 0.001 VS p = 0.029). All ALK-positive patients had 3 or more ALK-rearranged CTC per ml of blood. Less than 3 ALK-rearranged CTC was detected in ALK-negative patients. NanoVelcro can detect the ALK–rearranged status with consistent sensitivity and specificity compared to biopsy test. Furthermore, the ALK-rearranged CTC ratio correlated to the pTNM stage in ALK-positive patients. Following up showed that CTCs counting by NanoVelcro was more stable and reliable in evaluating the efficacy of Clozotinib both in the short and long run compared with CellSearch. Changing of NanoVlecro CTC counts could accurately reflect disease progression.ConclusionNanoVelcro provides a sensitive method for CTC counts and characterization in advanced NSCLC. ALK-rearrangement can be detected in CTCs collected from advanced NSCLC patients by NanoVelcro, facilitating diagnostic test and prognosis analysis, most importantly offering one noninvasive method for real-time monitoring of treatment reaction.