Complementary Sequential Circulating Tumor Cell (CTC) and Cell-Free Tumor DNA (ctDNA) Profiling Reveals Metastatic Heterogeneity and Genomic Changes in Lung Cancer and Breast Cancer

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Aug 2

PMID 34336686

Citations 12

Authors

Say Li Kong

Xingliang Liu

Swee Jin Tan

Joyce A Tai

Ler Yee Phua

Huay Mei Poh

Trifanny Yeo

Yong Wei Chua

Yu Xuan Haw

Wen Huan Ling

Raymond Chee Hui Ng

Tira J Tan

Kiley Wei Jen Loh

Daniel Shao-Weng Tan

Quan Sing Ng

Mei Kim Ang

Chee Keong Toh

Yi Fang Lee

Chwee Teck Lim

Tony Kiat Hon Lim

Axel M Hillmer

Yoon Sim Yap

Wan-Teck Lim

Affiliations

Soon will be listed here.

Abstract

Introduction: Circulating tumor cells (CTCs) and cell-free tumor DNA (ctDNA) are tumor components present in circulation. Due to the limited access to both CTC enrichment platforms and ctDNA sequencing in most laboratories, they are rarely analyzed together.

Methods: Concurrent isolation of ctDNA and single CTCs were isolated from lung cancer and breast cancer patients using the combination of size-based and CD45-negative selection method DropCell platform. We performed targeted amplicon sequencing to evaluate the genomic heterogeneity of CTCs and ctDNA in lung cancer and breast cancer patients.

Results: Higher degrees of genomic heterogeneity were observed in CTCs as compared to ctDNA. Several shared alterations present in CTCs and ctDNA were undetected in the primary tumor, highlighting the intra-tumoral heterogeneity of tumor components that were shed into systemic circulation. Accordingly, CTCs and ctDNA displayed higher degree of concordance with the metastatic tumor than the primary tumor. The alterations detected in circulation correlated with worse survival outcome for both lung and breast cancer patients emphasizing the impact of the metastatic phenotype. Notably, evolving genetic signatures were detected in the CTCs and ctDNA samples during the course of treatment and disease progression.

Conclusions: A standardized sample processing and data analysis workflow for concurrent analysis of CTCs and ctDNA successfully dissected the heterogeneity of metastatic tumor in circulation as well as the progressive genomic changes that may potentially guide the selection of appropriate therapy against evolving tumor clonality.

Citing Articles

The Combined Assessment of CTC and Status in Liquid Biopsy Samples Enhances the Clinical Value of Prediction in Metastatic Breast Cancer.

Szostakowska-Rodzos M, Grzybowska E, Mysliwy I, Zub R, Jagiello-Gruszfeld A, Rubach M Int J Mol Sci. 2025; 26(5).

PMID: 40076662 PMC: 11900918. DOI: 10.3390/ijms26052038.

Dual Biomarker Strategies for Liquid Biopsy: Integrating Circulating Tumor Cells and Circulating Tumor DNA for Enhanced Tumor Monitoring.

Moon G, Dalkiran B, Park H, Shin D, Son C, Choi J Biosensors (Basel). 2025; 15(2).

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Advances in microfluidic platforms for tumor cell phenotyping: from bench to bedside.

Joshi R, Ahmadi H, Gardner K, Bright R, Wang W, Li W Lab Chip. 2025; 25(5):856-883.

PMID: 39774602 PMC: 11859771. DOI: 10.1039/d4lc00403e.

Melanoma's New Frontier: Exploring the Latest Advances in Blood-Based Biomarkers for Melanoma.

Prkacin I, Mokos M, Ferara N, Situm M Cancers (Basel). 2025; 16(24.

PMID: 39766118 PMC: 11727356. DOI: 10.3390/cancers16244219.

Decoding the Dynamics of Circulating Tumor DNA in Liquid Biopsies.

Turabi K, Klute K, Radhakrishnan P Cancers (Basel). 2024; 16(13).

PMID: 39001494 PMC: 11240538. DOI: 10.3390/cancers16132432.

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