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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2025-03-01
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| author | Kazuaki Chikamatsu Hideyuki Takahashi Hiroe Tada Miho Uchida Shota Ida Yuichi Tomidokoro Masaomi Motegi |
| author_facet | Kazuaki Chikamatsu Hideyuki Takahashi Hiroe Tada Miho Uchida Shota Ida Yuichi Tomidokoro Masaomi Motegi |
| author_sort | Kazuaki Chikamatsu |
| collection | DOAJ |
| description | 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. |
| format | Article |
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| issn | 1467-3037 1467-3045 |
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| spelling | doaj-art-914345c49d834fc2acf75c909fd462ef2025-08-20T02:17:20ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-03-0147424010.3390/cimb47040240Circulating Tumor Cells in Head and Neck Squamous-Cell Carcinoma Exhibit Distinct Properties Based on Targeted Epithelial-Related MarkersKazuaki Chikamatsu0Hideyuki Takahashi1Hiroe Tada2Miho Uchida3Shota Ida4Yuichi Tomidokoro5Masaomi Motegi6Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi 371-8511, Gunma, JapanDepartment of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi 371-8511, Gunma, JapanDepartment of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi 371-8511, Gunma, JapanDepartment of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi 371-8511, Gunma, JapanDepartment of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi 371-8511, Gunma, JapanDepartment of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi 371-8511, Gunma, JapanDepartment of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi 371-8511, Gunma, JapanThe 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.https://www.mdpi.com/1467-3045/47/4/240circulating tumor cellhead and neck squamous-cell carcinomaepithelial cell adhesion moleculeepidermal growth factor receptorc-METliquid biopsy |
| spellingShingle | Kazuaki Chikamatsu Hideyuki Takahashi Hiroe Tada Miho Uchida Shota Ida Yuichi Tomidokoro Masaomi Motegi Circulating Tumor Cells in Head and Neck Squamous-Cell Carcinoma Exhibit Distinct Properties Based on Targeted Epithelial-Related Markers Current Issues in Molecular Biology circulating tumor cell head and neck squamous-cell carcinoma epithelial cell adhesion molecule epidermal growth factor receptor c-MET liquid biopsy |
| title | Circulating Tumor Cells in Head and Neck Squamous-Cell Carcinoma Exhibit Distinct Properties Based on Targeted Epithelial-Related Markers |
| title_full | Circulating Tumor Cells in Head and Neck Squamous-Cell Carcinoma Exhibit Distinct Properties Based on Targeted Epithelial-Related Markers |
| title_fullStr | Circulating Tumor Cells in Head and Neck Squamous-Cell Carcinoma Exhibit Distinct Properties Based on Targeted Epithelial-Related Markers |
| title_full_unstemmed | Circulating Tumor Cells in Head and Neck Squamous-Cell Carcinoma Exhibit Distinct Properties Based on Targeted Epithelial-Related Markers |
| title_short | Circulating Tumor Cells in Head and Neck Squamous-Cell Carcinoma Exhibit Distinct Properties Based on Targeted Epithelial-Related Markers |
| title_sort | circulating tumor cells in head and neck squamous cell carcinoma exhibit distinct properties based on targeted epithelial related markers |
| topic | circulating tumor cell head and neck squamous-cell carcinoma epithelial cell adhesion molecule epidermal growth factor receptor c-MET liquid biopsy |
| url | https://www.mdpi.com/1467-3045/47/4/240 |
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