임수빈 (Su Bin Lim) National University of Singapore
CV (220.10 KB)
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Proc. Natl. Acad. Sci. USA, First published August 15, 2019 | https://doi.org/10.1073/pnas.1907904116
Addressing cellular heterogeneity in tumor and circulation for refined prognostication
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Abstract

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.

microfluidics, circulating biomarkers, tumor heterogeneity

Category: Medicine
등록일 2019.08.19
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