Abstract
Patients with hepatocellular carcinoma (HCC) release tumor cells to the bloodstream, which can be detected using cell surface markers. Despite numerous reports suggest a direct correlation between the number of circulating tumor cells (CTCs) and poor clinical outcomes, few studies have provided a thorough molecular characterization of CTCs. Due to the limited access to tissue samples in patients at advanced stages of HCC, it is crucial to develop new technologies to identify HCC cancer drivers in routine clinical conditions. Here, we describe a method that sequentially combines image flow cytometry and high density single-cell mRNA sequencing to identify CTCs in HCC patients. Genome wide expression profiling of CTCs using this approach demonstrates CTC heterogeneity and helps detect known oncogenic drivers in HCC such as IGF2. This integrated approach provides a novel tool for biomarker development in HCC using liquid biopsy.
Highlights
The concept of liquid biopsy, which entails the analysis of tumor components released to the bloodstream (i.e., DNA and tumor cells), has revolutionized oncology[1]
Most of the studies exploring circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) have shown a direct correlation between higher CTC number and poor clinical outcomes[5]
Molecular characterization, which is critical to use CTCs analysis as a proxy to interrogate dominant tumor molecular alterations. This concept was recently shown in a patient with metastatic breast cancer using whole genome sequencing (WGS) in CTCs6, which allowed detecting known driver mutations in the CTC compartment
Summary
The concept of liquid biopsy, which entails the analysis of tumor components released to the bloodstream (i.e., DNA and tumor cells), has revolutionized oncology[1]. The 3 candidate CTCs isolated from both patients shared 12% of their top 100 expressed genes (TTR, FABP1, GSTA1, APOH, FGB, HULC, ALB, APOA2, SEPP1, APOC1, HPD and ORM1), which increased our confidence of efficient CTC detection.
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