肿瘤细胞治疗研究
英文原题：Protease-Activated Receptor 1 (PAR1) Expression Contributes to HPV-Associated Oropharyngeal Cancer Prognosis.
我们的结果表明，PAR1表达影响HPV相关口咽癌的预后和复发率。
人乳头瘤病毒（HPV）相关口咽癌偶尔预后较差，因此进行预后风险分层至关重要。蛋白酶激活受体-1（PAR1）参与癌变过程，其表达受含α-抑制蛋白结构域蛋白3（ARRDC3）调控。它还参与肿瘤微环境。我们试图评估PAR1、ARRDC3和TIL（肿瘤浸润淋巴细胞）评分在口咽癌、下咽癌和子宫颈癌患者中的预测能力，作为HPV相关口咽癌的对照。
对79例口咽癌、44例下咽癌和42例子宫颈癌样本进行了p16、ARRDC3和PAR1表达的免疫组化分析。评估TIL评分，并根据浸润程度分为以下组别：低：0-10%，中：20-40%，高：> 50%。对于预后分析，将这三组按低、中、高类别进行评估，或者以中位值作为截断值分为两组。
p16在44例（56%）口咽癌、8例（18%）下咽癌以及所有子宫颈癌样本中表达。ARRDC3在39例（49%）口咽癌、25例（57%）下咽癌和23例（55%）子宫颈癌样本中检测到。PAR1在45例（57%）口咽癌、22例（50%）下咽癌和22例（50%）子宫颈癌样本中表达。诊断为p16阳性口咽癌的患者与诊断为p16阴性癌的患者相比，预后显著改善。PAR1阴性病例与阳性病例相比，预后显著改善（疾病特异性生存[DSS]和阴性病例（无病生存[DFS]）。多因素分析显示，ARRDC3阳性病例的DSS预后明显优于p16阴性口咽癌患者。在p16阳性口咽癌患者中，PAR1阳性患者预后较差。就DFS而言，PAR1阳性和p16阴性口咽癌患者的复发率比PAR1阴性和p16阴性口咽癌患者高35倍。
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 cancer had a poor prognosis. With respect to DFS, patients with PAR1-positive and p16-negative oropharyngeal cancer had a 35-fold higher recurrence rate than those with PAR1-negative and p16-negative oropharyngeal cancer. CONCLUSION: Our results suggest that PAR1 expression affects the prognosis and recurrence rate of HPV-associated oropharyngeal cancer.
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