Circulating Tumor Cells in Head and Neck Squamous-Cell Carcinoma Exhibit Distinct Properties Based on Targeted Epithelial-Related Markers

The detection of circulating tumor cells (CTCs) using immunoaffinity-based methods often relies on epithelial-related markers, which may bias the selection of CTCs and limit the biological information obtained, depending on the targeted antigens. Herein, we compared the molecular profiles and clinic...

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Main Authors: Kazuaki Chikamatsu, Hideyuki Takahashi, Hiroe Tada, Miho Uchida, Shota Ida, Yuichi Tomidokoro, Masaomi Motegi
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/47/4/240
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Summary:The detection of circulating tumor cells (CTCs) using immunoaffinity-based methods often relies on epithelial-related markers, which may bias the selection of CTCs and limit the biological information obtained, depending on the targeted antigens. Herein, we compared the molecular profiles and clinical significance of CTCs based on the expression of epithelial-related markers (<i>EPCAM</i>, <i>EGFR</i>, and <i>MET</i>) in patients with head and neck squamous-cell carcinoma (HNSCC). CTCs were detected using density gradient separation and CD45-negative selection, followed by quantitative PCR for epithelial-related marker expression. Expression profiles of epithelial–mesenchymal transition (EMT)-related (<i>VIM</i>, <i>CDH1</i>, <i>CDH2</i>, <i>SNAI1</i>, <i>ZEB1</i>, <i>ZEB2</i>, and <i>TWIST1</i>) and immune-regulatory (<i>CD274</i> and <i>PDCD1LG2</i>) genes were compared. Moreover, the association between marker expression and clinical factors was analyzed. Among the 60 patients with CTCs, 48 (80.0%), 20 (33.3%), and 31 (51.7%) were positive for <i>EPCAM</i>, <i>EGFR</i>, and <i>MET</i>, respectively. A significant correlation was observed between CTCs expressing <i>EPCAM</i> and <i>EGFR</i>. CTCs expressing distinct markers showed differing EMT-related and immune-regulatory gene expression. <i>EPCAM</i>+ CTCs were associated with advanced-stage disease, while <i>EGFR</i>+ CTCs were correlated with locoregional relapse and shorter progression-free survival (<i>p</i> = 0.007; hazard ratio = 3.254). Patients with <i>EPCAM</i>/<i>EGFR</i> double-positive CTCs had the poorest prognosis. These findings emphasize the importance of marker selection in liquid biopsy technologies and highlight the need for improved detection methods and the further investigation of CTC biology.
ISSN:1467-3037
1467-3045