To improve management of head and neck squamous cell carcinoma patients, we need to increase our understanding of carcinogenesis, to identify biomarkers, and drug targets. This study aimed to identify novel biomarkers by providing transcriptomics profiles of matched primary tumors, lymph node metastasis, and non-malignant tissue of 20 HNSCC patients as well as by bioinformatic analyses of a TCGA HNSCC cohort, comprising 554 patients. We provide cancer cell signaling networks differentially expressed in tumors versus metastases, such as mesenchymal–epithelial transition, and structural integrity networks. As a proof of principle study, we exploited the data sets and performed functional analyses of a novel cytokeratin, cytokeratin24 (cKRT24), which had not been described as biomarker for tumors before. Survival analysis revealed that low cKRT24 expression correlated with poor overall survival in HNSCC. Experimentally, downregulation of cKRT24 in primary tumors, metastases, and HNSCC cell lines was verified on mRNA and protein level. Cloning and ectopic overexpression of cKRT24 not only affected viability and growth of HNSSC cell lines, but also inhibited tumor growth in murine xenograft studies. We conclude that cKRT24 functions as a tumor suppressor in HNSCC, and may serve as an additional prognostic biomarker and novel target to support current HNSCC treatments.

中文翻译：

---

将细胞角蛋白 24 鉴定为治疗头颈癌的肿瘤抑制因子

为了改善对头颈部鳞状细胞癌患者的管理，我们需要增加对致癌作用的了解，以确定生物标志物和药物靶点。本研究旨在通过提供 20 名 HNSCC 患者匹配的原发性肿瘤、淋巴结转移和非恶性组织的转录组学谱以及对TCGAHNSCC 队列，包括 554 名患者。我们提供在肿瘤中差异表达的癌细胞信号网络相对转移，例如间充质-上皮转化和结构完整性网络。作为原理研究的证明，我们利用数据集并对一种新的细胞角蛋白 cytokeratin24 (cKRT24) 进行了功能分析，这种细胞角蛋白以前未被描述为肿瘤的生物标志物。生存分析显示，低 cKRT24 表达与 HNSCC 较差的总体生存率相关。实验上，在 mRNA 和蛋白质水平上验证了原发性肿瘤、转移灶和 HNSCC 细胞系中 cKRT24 的下调。cKRT24 的克隆和异位过表达不仅影响 HNSSC 细胞系的活力和生长，而且还在小鼠异种移植研究中抑制肿瘤生长。我们得出结论，cKRT24 在 HNSCC 中充当肿瘤抑制因子，