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  • 标题:Addressing cellular heterogeneity in tumor and circulation for refined prognostication
  • 本地全文:下载
  • 作者:Su Bin Lim ; Trifanny Yeo ; Wen Di Lee
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2019
  • 卷号:116
  • 期号:36
  • 页码:17957-17962
  • DOI:10.1073/pnas.1907904116
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要: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.
  • 关键词:microfluidics ; circulating biomarkers ; tumor heterogeneity
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