モリヤ　タクヤ   Takuya Moriya   森谷　卓也    所属   川崎医科大学  医学部 臨床医学　病理学    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Protease-Activated Receptor 1 (PAR1) Expression Contributes to HPV-Associated Oropharyngeal Cancer Prognosis.
掲載誌名	正式名：Head and neck pathology 略　 称：Head Neck Pathol ISSNコード：19360568/1936055X
著者・共著者	Yoshinori Fujita, Yujiro Fukuda, Fumiaki Sanuki, Isao Irei, Yasumasa Monobe, Masako Uno, Takeshi Akisada, Koichiro Shimoya, Hirotaka Hara, Takuya Moriya
担当区分	最終著者
発行年月	2023/07/24
概要	BACKGROUND:Human papillomavirus (HPV)-associated oropharyngeal cancer occasionally has a poor prognosis, making prognostic risk stratification crucial. Protease-activated receptor-1 (PAR1) is involved in carcinogenesis, and its expression is regulated by alpha-arrestin domain-containing protein 3 (ARRDC3). It is also involved in the tumor microenvironment. We sought to evaluate the predictive ability of PAR1, ARRDC3, and tumor-infiltrating lymphocyte (TIL) scores in patients with oropharyngeal, hypopharyngeal, and uterine cervical cancers, serving as comparators for HPV-associated oropharyngeal cancer.METHODS:Immunohistochemical analysis of p16, ARRDC3, and PAR1 expression was performed on 79 oropharyngeal, 44 hypopharyngeal, and 42 uterine cervical cancer samples. The TIL scores were assessed and classified into the following groups based on invasion: low: 0-10%, medium: 20-40%, and high: > 50%. For prognostic analysis, the three groups were evaluated by dividing them into low, medium, and high categories, or alternatively into two groups using the median value as the cutoff.RESULTS:p16 was expressed in 44 (56%) oropharyngeal, 8 (18%) hypopharyngeal, and all uterine cervical cancer samples. ARRDC3 was detected in 39 (49%) oropharyngeal, 25 (57%) hypopharyngeal, and 23 (55%) uterine cervical cancer samples. PAR1 was expressed in 45 (57%) oropharyngeal, 22 (50%) hypopharyngeal, and 22 (50%) uterine cervical cancer samples. Patients diagnosed with p16-positive oropharyngeal cancer had a substantially improved prognosis compared to those diagnosed with p16-negative cancer. The PAR1-negative cases had a considerably improved prognosis compared to the positive cases (disease-specific survival [DSS] and -negative cases (disease-free survival [DFS]). Multivariate analysis revealed that ARRDC3-positive cases had an appreciably better DSS prognosis than patients with p16-negative oropharyngeal cancers. PAR1-positive patients among patients with p16-positive oropharyngeal can
DOI	10.1007/s12105-023-01567-5
PMID	37486532