HPV 阴性且具有不良病理特征的头颈部癌症具有与生存相关的特定分子变化。
HPV-negative head and neck cancers with adverse pathological features carry specific molecular changes that are associated with survival.
机构信息
Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada.
Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada.
出版信息
Head Neck. 2024 Feb;46(2):353-366. doi: 10.1002/hed.27591. Epub 2023 Dec 7.
BACKGROUND
Adverse pathological features following surgery in head and neck squamous cell carcinoma (HNSCC) are strongly associated with survival and guide adjuvant therapy. We investigated molecular changes associated with these features.
METHODS
We downloaded data from the Cancer Genome Atlas and Cancer Proteome Atlas HNSCC cohorts. We compared tumors positive versus negative for perineural invasion (PNI), lymphovascular invasion (LVI), extracapsular spread (ECS), and positive margins (PSM), with multivariable analysis.
RESULTS
All pathological features were associated with poor survival, as were the following molecular changes: low cyclin E1 (HR = 1.7) and high PKC-alpha (HR = 1.8) in tumors with PNI; six of 13 protein abundance changes with LVI; greater tumor hypoxia and high Raptor (HR = 2.0) and Rictor (HR = 1.6) with ECS; and low p38 (HR = 2.3), high fibronectin (HR = 1.6), low annexin A1 (HR = 3.1), and high caspase-9 (HR = 1.6) abundances with PSM.
CONCLUSIONS
Pathological features in HNSCC carry specific molecular changes that may explain their poor prognostic associations.
背景
头颈部鳞状细胞癌（HNSCC）手术后的不良病理特征与生存密切相关，并指导辅助治疗。我们研究了与这些特征相关的分子变化。
方法
我们从癌症基因组图谱和癌症蛋白质组图谱 HNSCC 队列中下载了数据。我们使用多变量分析比较了神经周围浸润（PNI）、淋巴血管浸润（LVI）、细胞外扩散（ECS）和阳性切缘（PSM）阳性与阴性的肿瘤。
结果
所有的病理特征都与不良预后相关，同时还存在以下分子变化：PNI 肿瘤中 cyclin E1 水平较低（HR=1.7）和 PKC-alpha 水平较高（HR=1.8）；LVI 存在 13 种蛋白质丰度变化中的 6 种；肿瘤缺氧程度更高，Raptor（HR=2.0）和 Rictor（HR=1.6）水平较高与 ECS 相关；PSM 存在 p38 水平较低（HR=2.3）、纤连蛋白水平较高（HR=1.6）、膜联蛋白 A1 水平较低（HR=3.1）和 caspase-9 水平较高（HR=1.6）。
结论
HNSCC 的病理特征具有特定的分子变化，这可能解释了它们与不良预后的关联。
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