An Indocyanine Green-Based Liquid Biopsy Test for Circulating Tumor Cells for Pediatric Liver Cancer

Authors

• Andres F Espinoza
• Pavan Kureti
• Roma H Patel
• Susan L Do
• Saiabhiroop R Govindu
• Bryan W Armbruster
• Martin Urbicain
• Kalyani R Patel
• Dolores Lopez-Terrada
• Sanjeev A Vasudevan
• Sarah E Woodfield

Language

English

Publication Date

6-1-2024

Journal

Hepatology Communications

DOI

10.1097/HC9.0000000000000435

PMID

38727682

PMCID

PMC11093570

PubMedCentral® Posted Date

5-10-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Hepatoblastoma and HCC are the most common malignant hepatocellular tumors seen in children. The aim of this study was to develop a liquid biopsy test for circulating tumor cells (CTCs) for these tumors that would be less invasive and provide real-time information about tumor response to therapy.

Methods: For this test, we utilized indocyanine green (ICG), a far-red fluorescent dye used clinically to identify malignant liver cells during surgery. We assessed ICG accumulation in cell lines using fluorescence microscopy and flow cytometry. For our CTC test, we developed a panel of liver tumor-specific markers, including ICG, Glypican-3, and DAPI, and tested it with cell lines and noncancer control blood samples. We then used this panel to analyze whole-blood samples for CTC burden with a cohort of 15 patients with hepatoblastoma and HCC and correlated with patient characteristics and outcomes.

Results: We showed that ICG accumulation is specific to liver cancer cells, compared to nonmalignant liver cells, non-liver solid tumor cells, and other nonmalignant cells, and can be used to identify liver tumor cells in a mixed population of cells. Experiments with the ICG/Glypican-3/DAPI panel showed that it specifically tagged malignant liver cells. Using patient samples, we found that CTC burden from sequential blood samples from the same patients mirrored the patients' responses to therapy.

Conclusions: Our novel ICG-based liquid biopsy test for CTCs can be used to specifically detect and quantify CTCs in the blood of pediatric patients with liver cancer.

Keywords

Humans, Indocyanine Green, Neoplastic Cells, Circulating, Liquid Biopsy, Liver Neoplasms, Child, Female, Male, Child, Preschool, Hepatoblastoma, Carcinoma, Hepatocellular, Cell Line, Tumor, Biomarkers, Tumor, Infant, Adolescent, Coloring Agents

Published Open-Access

yes

Recommended Citation

Espinoza, Andres F; Kureti, Pavan; Patel, Roma H; et al., "An Indocyanine Green-Based Liquid Biopsy Test for Circulating Tumor Cells for Pediatric Liver Cancer" (2024). Faculty, Staff and Students Publications. 8318.
https://digitalcommons.library.tmc.edu/baylor_docs/8318