Molecular profiling of single circulating tumor cells from lung cancer patients

Proc Natl Acad Sci U S A. 2016 Dec 27;113(52):E8379-E8386. doi: 10.1073/pnas.1608461113. Epub 2016 Dec 12.

Abstract

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.

Keywords: circulating tumor cells; microfluidics; rare-cell sorting; reverse transcription-PCR; single-cell analysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • 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 Neoplasms / blood*
  • Lung Neoplasms / pathology
  • Male
  • Microfluidics
  • Middle Aged
  • Mutation
  • Nanotechnology
  • Neoplastic Cells, Circulating*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Single-Cell Analysis

Substances

  • Biomarkers, Tumor
  • Leukocyte Common Antigens
  • PTPRC protein, human