Journal Article

Addressing cellular heterogeneity in tumor and circulation for refined prognostication

Yeo, Trifanny, Bhagat, Ali Asgar S., Lim, Chwee Teck, Tan, Swee Jin, Lim, Su Bin, Tan, Daniel Shao Weng, Di Lee, Wen, Lim, Wan-Teck

2019

Overview

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.

• Publisher: National Academy of Sciences
• Subject: Biological Sciences / Biomarkers, Tumor / Carcinoma, Non-Small-Cell Lung - etiology / Carcinoma, Non-Small-Cell Lung - mortality / Carcinoma, Non-Small-Cell Lung - pathology / Female / Gene expression / Heterogeneity / Humans / Immunohistochemistry / Lung cancer / Lung Neoplasms - etiology / Lung Neoplasms - mortality / Lung Neoplasms - pathology / Male / Medical Sciences / Metastases / Microfluidic Analytical Techniques / Microfluidics / Neoplasm Metastasis / Neoplasm Staging / Neoplasms - etiology / Neoplasms - mortality / Neoplasms - pathology / Neoplastic Cells, Circulating - pathology / Non-small cell lung carcinoma / Predictions / Prognosis / Risk / Signatures / Tumor cells / Tumor Microenvironment / Tumors