CYLD改变与人类乳头瘤病毒阳性头颈癌的转移及不良预后相关。
CYLD Alterations Are Associated With Metastasis and Poor Prognosis in Human Papilloma Virus-Positive Head and Neck Cancer.
作者信息
Cui Zhibin, Kang Hyunseok, Li Hua, Lee Eliot D, Lee Yoon Se, Peterson Christopher N, Long Steven R, Grandis Jennifer R, Johnson Daniel E
机构信息
Department of Otolaryngology-Head and Neck Surgery, University of California at San Francisco, San Francisco, California, USA.
Department of Medicine, University of California at San Francisco, San Francisco, California, USA.
出版信息
Head Neck. 2025 Feb;47(2):606-614. doi: 10.1002/hed.27944. Epub 2024 Sep 30.
BACKGROUND
Human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is an emerging epidemic and a subset of HPV-positive patients experience aggressive disease with metastases. The CYLD gene is frequently altered in HPV-positive HNSCC, but the role of these alterations in disease progression is poorly understood.
METHODS
We identified 11 HPV-positive HNSCC patients with CYLD alterations and assessed their clinical course. We also characterized a unique, HPV-positive, metastatic, HNSCC patient-derived xenograft (PDX).
RESULTS
All 11 patients developed metastasis with reduced overall survival when compared with metastatic HPV-positive patients with wild-type CYLD. The metastatic PDX harbored a CYLD mutation (S371*) and exhibited reduced expression of connexin 43, a potentially antimetastatic protein. We also investigated the functional impact of the S371* mutation, as well as 2 CYLD mutations from our 11-patient cohort.
CONCLUSION
Our findings indicate that alterations in CYLD in HPV-positive HNSCC are associated with metastasis and poor prognosis.
背景
人乳头瘤病毒（HPV）相关的头颈部鳞状细胞癌（HNSCC）是一种新出现的流行病，一部分HPV阳性患者会经历侵袭性疾病并发生转移。CYLD基因在HPV阳性的HNSCC中经常发生改变，但这些改变在疾病进展中的作用尚不清楚。
方法
我们确定了11例CYLD基因改变的HPV阳性HNSCC患者，并评估了他们的临床病程。我们还对一例独特的、HPV阳性、转移性HNSCC患者来源的异种移植瘤（PDX）进行了特征分析。
结果
与野生型CYLD的转移性HPV阳性患者相比，所有11例患者均发生转移且总生存期缩短。转移性PDX携带CYLD突变（S371*），并表现出连接蛋白43（一种潜在的抗转移蛋白）表达降低。我们还研究了S371*突变以及我们11例患者队列中的另外2种CYLD突变的功能影响。
结论
我们的研究结果表明，HPV阳性HNSCC中CYLD基因的改变与转移和不良预后相关。
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