Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama.
Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
Mol Cancer Res. 2016 Sep;14(9):883-91. doi: 10.1158/1541-7786.MCR-16-0114. Epub 2016 Jun 27.
Oral squamous cell carcinoma (OSCC) is a cancer subtype that lacks validated prognostic and therapeutic biomarkers, and human papillomavirus status has not proven beneficial in predicting patient outcomes. A gene expression pathway analysis was conducted using OSCC patient specimens to identify molecular targets that may improve management of this disease. RNA was isolated from 19 OSCCs treated surgically at the University of Alabama at Birmingham (UAB; Birmingham, AL) and evaluated using the NanoString nCounter system. Results were confirmed using the oral cavity subdivision of the Head and Neck Squamous Cell Carcinoma Cancer (HNSCC) study generated by The Cancer Genome Atlas (TCGA) Research Network. Further characterization of the in vitro phenotype produced by Notch pathway activation in HNSCC cell lines included gene expression, proliferation, cell cycle, migration, invasion, and radiosensitivity. In both UAB and TCGA samples, Notch pathway upregulation was significantly correlated with patient mortality status and with expression of the proinvasive gene FGF1 In vitro Notch activation in HNSCC cells increased transcription of FGF1 and induced a marked increase in cell migration and invasion, which was fully abrogated by FGF1 knockdown. These results reveal that increased Notch pathway signaling plays a role in cancer progression and patient outcomes in OSCC. Accordingly, the Notch-FGF interaction should be further studied as a prognostic biomarker and potential therapeutic target for OSCC.
Patients with squamous cell carcinoma of the oral cavity who succumb to their disease are more likely to have upregulated Notch signaling, which may mediate a more invasive phenotype through increased FGF1 transcription. Mol Cancer Res; 14(9); 883-91. ©2016 AACR.
口腔鳞状细胞癌（OSCC）是一种缺乏经过验证的预后和治疗生物标志物的癌症亚型，人乳头瘤病毒状态并未证明有利于预测患者的预后。使用 OSCC 患者标本进行了基因表达途径分析，以确定可能改善该疾病管理的分子靶标。从在阿拉巴马大学伯明翰分校（UAB；伯明翰，AL）接受手术治疗的 19 例 OSCC 中分离 RNA，并使用 NanoString nCounter 系统进行评估。使用由癌症基因组图谱（TCGA）研究网络生成的口腔细分的头颈部鳞状细胞癌（HNSCC）研究来确认结果。进一步表征 HNSCC 细胞系中 Notch 途径激活产生的体外表型，包括基因表达、增殖、细胞周期、迁移、侵袭和放射敏感性。在 UAB 和 TCGA 样本中，Notch 途径的上调与患者死亡率状态以及促侵袭基因 FGF1 的表达显著相关。体外 Notch 激活增加了 HNSCC 细胞中 FGF1 的转录，并诱导细胞迁移和侵袭显著增加，而 FGF1 敲低则完全阻断了这一作用。这些结果表明，Notch 途径信号的增加在 OSCC 中发挥作用，促进癌症进展和患者预后。因此， Notch-FGF 相互作用应作为 OSCC 的预后生物标志物和潜在治疗靶点进一步研究。 Mol Cancer Res；14（9）；883-91. ©2016 AACR.
