Molecular profiling of single circulating tumor cells from lung cancer patients

被引:76
|
作者
Park, Seung-min [1 ,2 ]
Wong, Dawson J. [3 ]
Ooi, Chin Chun [4 ]
Kurtz, David M. [2 ,5 ,6 ]
Vermesh, Ophir [1 ,2 ]
Aalipour, Amin [1 ,2 ]
Suh, Susie [7 ]
Pian, Kelsey L. [8 ]
Chabon, Jacob J. [9 ]
Lee, Sang Hun [10 ]
Jamali, Mehran [1 ]
Say, Carmen [11 ]
Carter, Justin N. [11 ]
Lee, Luke P. [10 ]
Kuschner, Ware G. [12 ,13 ]
Schwartz, Erich J. [14 ]
Shrager, Joseph B. [15 ]
Neal, Joel W. [6 ,16 ]
Wakelee, Heather A. [6 ,16 ]
Diehn, Maximilian [9 ,16 ,17 ]
Nair, Viswam S. [1 ,13 ,17 ]
Wang, Shan X. [3 ,8 ,17 ]
Gambhir, Sanjiv S. [1 ,2 ,17 ]
机构
[1] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Mol Imaging Program Stanford, Stanford, CA 94305 USA
[3] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA
[4] Stanford Univ, Dept Chem Engn, Stanford, CA 94305 USA
[5] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA
[6] Stanford Univ, Dept Med, Sch Med, Div Oncol, Stanford, CA 94305 USA
[7] Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA
[8] Stanford Univ, Dept Mat Sci & Engn, Stanford, CA 94305 USA
[9] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA
[10] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
[11] Stanford Univ, Dept Radiat Oncol, Sch Med, Stanford, CA 94305 USA
[12] Vet Affairs Palo Alto Hlth Care Syst, Pulm & Crit Care Med Sect, Palo Alto, CA 94304 USA
[13] Stanford Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Stanford, CA 94305 USA
[14] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA
[15] Stanford Univ, Dept Cardiothorac Surg, Sch Med, Stanford, CA 94305 USA
[16] Stanford Univ, Stanford Canc Inst, Sch Med, Stanford, CA 94305 USA
[17] Stanford Univ, Canary Ctr Stanford Canc Early Detect, Sch Med, Palo Alto, CA 94305 USA
关键词
circulating tumor cells; microfluidics; rare-cell sorting; reverse transcription-PCR; single-cell analysis; GROWTH-FACTOR RECEPTOR; REVERSE-TRANSCRIPTASE HTERT; MESSENGER-RNA; EGFR MUTATION; DIFFERENTIAL EXPRESSION; MARKER; BLOOD; MET; CAPTURE; QUANTIFICATION;
D O I
10.1073/pnas.1608461113
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Circulating tumor cells (CTCs) are established cancer biomarkers for the "liquid biopsy" of tumors. Molecular analysis of single CTCs, which recapitulate primary and metastatic tumor biology, remains challenging because current platforms have limited throughput, are expensive, and are not easily translatable to the clinic. Here, we report a massively parallel, multigene-profiling nanoplatform to compartmentalize and analyze hundreds of single CTCs. After high-efficiency magnetic collection of CTC from blood, a single-cell nanowell array performs CTC mutation profiling using modular gene panels. Using this approach, we demonstrated multigene expression profiling of individual CTCs from non-small-cell lung cancer (NSCLC) patients with remarkable sensitivity. Thus, we report a high-throughput, multiplexed strategy for single-cell mutation profiling of individual lung cancer CTCs toward minimally invasive cancer therapy prediction and disease monitoring.
引用
收藏
页码:E8379 / E8386
页数:8
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