Department of Biomedical and Clinical Sciences, Division of Sensory Organs and Communication, Linköping University, Region Östergötland, Sweden.
Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm.
Otol Neurotol. 2021 Jan;42(1):e94-e100. doi: 10.1097/MAO.0000000000002850.
Surgery remains the gold standard in cholesteatoma treatment. However, the rate of recurrence is significant and the development of new nonsurgical treatment alternatives is warranted. One of the possible molecular pathways to target is the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway.
To investigate the JAK/STAT pathway in the middle ear mucosa in patients with acquired cholesteatoma compared with middle ear mucosa from healthy controls.
Case-control study.
Linköping University Hospital, Sweden, and Karolinska Institutet, Stockholm, Sweden. Sampling period: February 2011 to December 2016.
Middle ear mucosa from 26 patients with acquired cholesteatoma undergoing tympanoplasty and mastoidectomy, and 27 healthy controls undergoing translabyrinthine surgery for vestibular schwannoma or cochlear implantation was investigated.
MAIN OUTCOMES/MEASURES: The expression of Interleukin-7 receptor alpha, JAK1, JAK2, JAK3, STAT5A, STAT5B, and suppressor of cytokine signaling-1 (SOCS1) were quantified using quantitative polymerase chain reaction. In addition, expression level of cyclin D2, transforming growth factor beta 1, thymic stromal lymphopoietin, CD3, and CD19 was evaluated.
In cholesteatoma-adjacent mucosa, SOCS1 was significantly upregulated (p= 0.0003) compared with healthy controls, whereas STAT5B was significantly downregulated (p = 0.0006). The expression of JAK1, JAK2, JAK3, and STAT5A did not differ significantly between groups.
To the best of our knowledge, this is the first article reporting dysregulation of the JAK/STAT pathway in cholesteatoma-adjacent mucosa. The main finding is that important players of the aforementioned pathway are significantly altered, namely SOCS1 is upregulated and STAT5B is downregulated compared with healthy controls.
手术仍然是胆脂瘤治疗的金标准。然而，复发率很高，有必要开发新的非手术治疗方法。可能的靶向分子途径之一是 Janus 激酶/信号转导和转录激活因子（JAK/STAT）途径。
与健康对照组相比，研究中耳黏膜中获得性胆脂瘤患者的 JAK/STAT 途径。
病例对照研究。
瑞典林雪平大学医院和斯德哥尔摩卡罗林斯卡学院。采样时间：2011 年 2 月至 2016 年 12 月。
接受鼓室成形术和乳突切除术的 26 例获得性胆脂瘤患者的中耳黏膜，以及 27 例因前庭神经鞘瘤或耳蜗植入而行迷路手术的健康对照者。
主要结果/措施：采用定量聚合酶链反应检测白细胞介素-7 受体 alpha、JAK1、JAK2、JAK3、STAT5A、STAT5B 和细胞因子信号转导抑制因子-1（SOCS1）的表达。此外，还评估了 cyclin D2、转化生长因子-β1、胸腺基质淋巴生成素、CD3 和 CD19 的表达水平。
在胆脂瘤旁黏膜中，SOCS1 的表达明显上调（p=0.0003），而 STAT5B 的表达明显下调（p=0.0006）。各组之间 JAK1、JAK2、JAK3 和 STAT5A 的表达无显著差异。
据我们所知，这是第一篇报道胆脂瘤旁黏膜 JAK/STAT 途径失调的文章。主要发现是，上述途径的重要参与者发生了显著改变，即与健康对照组相比，SOCS1 上调，STAT5B 下调。
