期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 36, 页码 17957-17962出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1907904116
关键词
microfluidics; circulating biomarkers; tumor heterogeneity
资金
- Institute for Health Innovation and Technology (iHealthtech) at NUS
- National Medical Research Council [NMRC/CSA/040/2012, NMRC/CSA-INV/0025/2017]
- NUS Graduate School for Integrative Sciences and Engineering
- Daewoong Foundation
- Mogam Science Scholarship Foundation
Despite pronounced genomic and transcriptomic heterogeneity in non-small-cell lung cancer (NSCLC) not only between tumors, but also within a tumor, validation of clinically relevant gene signatures for prognostication has relied upon single-tissue samples, including 2 commercially available multigene tests (MGTs). Here we report an unanticipated impact of intratumor heterogeneity (ITH) on risk prediction of recurrence in NSCLC, underscoring the need for a better genomic strategy to refine prognostication. By leveraging label-free, inertial-focusing microfluidic approaches in retrieving circulating tumor cells (CTCs) at single-cell resolution, we further identified specific gene signatures with distinct expression profiles in CTCs from patients with differing metastatic potential. Notably, a refined prognostic risk model that reconciles the level of ITH and CTC-derived gene expression data outperformed the initial classifier in predicting recurrence-free survival (RFS). We propose tailored approaches to providing reliable risk estimates while accounting for ITH-driven variance in NSCLC.
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