Kadletz Lorenz, Thurnher Dietmar, Wiebringhaus Robert, Erovic Boban M, Kotowski Ulana, Schneider Sven, Schmid Rainer, Kenner Lukas, Heiduschka Gregor
Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.
Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Graz, Graz, Austria.
Oral Oncol. 2017 Apr;67:109-118. doi: 10.1016/j.oraloncology.2017.02.007. Epub 2017 Feb 27.
So far, no data is available on the role of the tumor stem cell marker doublecortin-like kinase 1 (DCLK1) in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to evaluate DCLK1 expression in HNSCC patients that underwent surgery and postoperative radiotherapy, and to assess its potential as a therapeutic target in vitro.
We immunohistochemically stained for DCLK1 in 127 sections of HNSCC samples obtained during surgery of HNSCC patients and correlated the expression to patients' overall- and disease-free survival, as well as human papilloma virus (HPV) status. Additionally, we compared our survival data with data obtained from The Cancer Genome Atlas (TCGA). The effects of the DCLK1 inhibitor LRRK-2-in-1 on HNSCC cell lines alone and in combination with irradiation.
Expression of DCLK1 in 127 patients was associated with poor survival. In particular, DCLK1 expression had a significant impact on survival of oropharyngeal carcinoma patients. Specifically, DCLK1/HPV patients had the worst prognosis after simultaneous assessment of DCLK1 and HPV status in comparison to the other three possible DCLK1/HPV constellations. Higher levels of DCLK1 mRNA were also associated with poor clinical outcome. Inhibition of DCLK1 in our HNSCC cell lines led to growth arrest and induction of apoptosis. The combination of DCLK1 inhibition with irradiation had a synergistic effect.
Firstly, DCLK1 is a prognostic biomarker for shortened survival. Secondly, through inhibition of DCLK1, it may serve as a therapeutic target as well.
到目前为止，尚无关于肿瘤干细胞标志物双皮质素样激酶1（DCLK1）在头颈部鳞状细胞癌（HNSCC）中作用的数据。本研究的目的是评估DCLK1在接受手术和术后放疗的HNSCC患者中的表达，并在体外评估其作为治疗靶点的潜力。
我们对127例HNSCC患者手术期间获得的HNSCC样本切片进行DCLK1免疫组化染色，并将其表达与患者的总生存期和无病生存期以及人乳头瘤病毒（HPV）状态相关联。此外，我们将我们的生存数据与从癌症基因组图谱（TCGA）获得的数据进行比较。研究DCLK1抑制剂LRRK-2-in-1单独及与放疗联合对HNSCC细胞系的影响。
127例患者中DCLK1的表达与较差的生存率相关。特别是，DCLK1的表达对口咽癌患者的生存有显著影响。具体而言，与其他三种可能的DCLK1/HPV组合相比，同时评估DCLK1和HPV状态时，DCLK1/HPV患者的预后最差。较高水平的DCLK1 mRNA也与不良临床结果相关。在我们的HNSCC细胞系中抑制DCLK1导致生长停滞和凋亡诱导。DCLK1抑制与放疗联合具有协同作用。
首先，DCLK1是生存期缩短的预后生物标志物。其次，通过抑制DCLK1，它也可能作为治疗靶点。
