Molecular profiling of single circulating tumor cells from lung cancer patients

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 tra...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 113; no. 52; pp. E8379 - E8386
Main Authors:	Park, Seung-min, Wong, Dawson J., Ooi, Chin Chun, Kurtz, David M., Vermesh, Ophir, Aalipour, Amin, Suh, Susie, Pian, Kelsey L., Chabon, Jacob J., Lee, Sang Hun, Jamali, Mehran, Say, Carmen, Carter, Justin N., Lee, Luke P., Kuschner, Ware G., Schwartz, Erich J., Shrager, Joseph B., Neal, Joel W., Wakelee, Heather A., Diehn, Maximilian, Nair, Viswam S., Wang, Shan X., Gambhir, Sanjiv S.
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 27-12-2016
Series:	PNAS Plus
Subjects:	Adult Aged Biological Sciences Biomarkers Biomarkers, Tumor - blood Biopsy Cancer therapies Carcinoma, Non-Small-Cell Lung - blood Carcinoma, Non-Small-Cell Lung - pathology Cell Count Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Leukocyte Common Antigens - blood Lung cancer Lung Neoplasms - blood Lung Neoplasms - pathology Male Microfluidics Middle Aged Mutation Nanotechnology Neoplastic Cells, Circulating Physical Sciences PNAS Plus Reverse Transcriptase Polymerase Chain Reaction Single-Cell Analysis Tumors rare-cell sorting reverse transcription-PCR circulating tumor cells microfluidics single-cell analysis
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 1S.-m.P., D.J.W., and C.C.O. contributed equally to this work. Edited by John A. Rogers, University of Illinois, Urbana, IL, and approved October 28, 2016 (received for review May 27, 2016) Author contributions: S.-m.P., D.J.W., C.C.O., D.M.K., O.V., S.H.L., L.P.L., M.D., V.S.N., S.X.W., and S.S.G. designed research; S.-m.P., D.J.W., C.C.O., S.S., K.L.P., and S.S.G. performed research; S.-m.P., D.J.W., C.C.O., D.M.K., O.V., A.A., S.S., J.J.C., M.J., C.S., J.N.C., W.G.K., J.B.S., J.W.N., H.A.W., M.D., V.S.N., S.X.W., and S.S.G. contributed new reagents/analytic tools; S.-m.P., D.J.W., C.C.O., O.V., A.A., S.S., K.L.P., J.J.C., E.J.S., M.D., V.S.N., S.X.W., and S.S.G. analyzed data; and S.-m.P., D.J.W., C.C.O., V.S.N., S.X.W., and S.S.G. wrote the paper.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.1608461113