Molecular phenotypes of circulating tumor cells and efficacy of nivolumab treatment in patients with head and neck squamous cell carcinoma
| Autor: | Kazuaki Chikamatsu, Shota Ida, Yurino Nagata, Toshiyuki Matsuyama, Miho Uchida, Masato Shino, Ikko Mito, Hideyuki Takahashi, Reika Kawabata-Iwakawa, Hiroe Tada |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Oncology Homeobox protein NANOG medicine.medical_specialty Science Cancer immunotherapy Article Tumour biomarkers 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine Circulating tumor cell Cyclin D1 Internal medicine Biomarkers Tumor medicine Humans Head and neck cancer Aged Multidisciplinary biology Squamous Cell Carcinoma of Head and Neck business.industry CD44 Middle Aged Proto-Oncogene Proteins c-met Epithelial Cell Adhesion Molecule Neoplastic Cells Circulating medicine.disease Head and neck squamous-cell carcinoma ErbB Receptors ALDH1A1 Nivolumab 030104 developmental biology Real-time polymerase chain reaction Head and Neck Neoplasms 030220 oncology & carcinogenesis biology.protein Medicine Female business |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-8 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-78741-0 |
| Popis: | The emergence of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Biomarkers of the therapeutic efficacy of ICIs have been extensively investigated. In this study, we aimed to analyze whether molecular phenotypes of circulating tumor cells (CTCs) are associated with treatment responses and clinical outcomes in patients with R/M HNSCC treated with nivolumab. Peripheral blood samples were collected before treatment initiation and after four infusions of nivolumab. CTCs isolated by depletion of CD45-positive cells were analyzed to determine the expression of EPCAM, MET, KRT19, and EGFR using real-time quantitative polymerase chain reaction. CTC-positive samples were analyzed to determine the expression of PIK3CA, CCND1, SNAI1, VIM, ZEB2, CD44, NANOG, ALDH1A1, CD47, CD274, and PDCD1LG2. Of 30 patients treated with nivolumab, 28 (93.3%) were positive for CTCs. In 20 CTC-positive patients, molecular alterations in CTCs before and after nivolumab treatment were investigated. Patients with MET-positive CTCs had significantly shorter overall survival than those with MET-negative CTCs (p = 0.027). The expression level of CCND1 in CTCs of disease-controlled patients was significantly higher than that of disease-progressed patients (p = 0.034). In disease-controlled patients, the expression level of CCND1 in CTCs significantly decreased after nivolumab treatment (p = 0.043). The NANOG expression in CTCs was significantly increased in disease-controlled patients after nivolumab treatment (p = 0.036). Our findings suggest that the molecular profiling of CTCs is a promising tool to predict the treatment efficacy of nivolumab. |
| Databáze: | OpenAIRE |
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