Infections and Cancer Laboratory/Cancer Epidemiology Research Program. Catalan Institute of Oncology (ICO) and Bellvitge Institute of Biomedical Research (IDIBELL), Barcelona, Spain.
Centro de Investigación Biomédica en Red en Cáncer (CIBER-ONC), Madrid, Spain.
Head Neck. 2019 Jun;41(6):1830-1845. doi: 10.1002/hed.25623. Epub 2019 Jan 16.
We aimed at identifying molecular markers predictive of clinical outcome in patients with head and neck cancer based on the expression profile of cells showing epithelial-like (EL) or mesenchymal-like (ML) phenotypes.
We analyzed the association between EL and ML cells and migration, drug resistance, or tumor growth. The differential gene expression profile between cell types was used to build a model to stratify patients according to survival.
EL cells were sensitive to cisplatin and cetuximab, showed low migration, and generated squamous differentiated tumors in mouse. A differential 93-gene expression signature between ML and EL cells was used to build a three-gene (EFS, GPX2, and SPRR1A) survival model by analyzing the RNA-seq data of the TCGA-HNSC project. Its prognostic value was confirmed in two independent cohorts.
EFS, GPX2, and SPRR1A are prognostic markers able to distinguish clinical outcome among subtypes sharing an EL phenotype.
我们旨在根据表现出上皮样 (EL) 或间充质样 (ML) 表型的细胞的表达谱,鉴定出与头颈部癌症患者临床结局相关的分子标志物。
我们分析了 EL 和 ML 细胞与迁移、耐药性或肿瘤生长之间的关联。利用细胞类型之间的差异基因表达谱构建了一个模型,根据生存情况对患者进行分层。
EL 细胞对顺铂和西妥昔单抗敏感,迁移能力低,在小鼠中产生鳞状分化肿瘤。通过分析 TCGA-HNSC 项目的 RNA-seq 数据,使用 ML 和 EL 细胞之间的差异 93 个基因表达特征构建了一个由三个基因(EFS、GPX2 和 SPRR1A)组成的生存模型。该模型的预后价值在两个独立队列中得到了验证。
EFS、GPX2 和 SPRR1A 是能够区分具有 EL 表型的亚型之间临床结局的预后标志物。