National University of Singapore

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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

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논문정보   
- 형식: Research article
- 게재일: 2019년 08월 (BRIC 등록일 2019-08-19)
- 연구진: 국외연구진
- 분야: Medicine
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