Department of Otorhinolaryngology, University of Duisburg-Essen, Essen, Germany.
PLoS One. 2013;8(2):e56420. doi: 10.1371/journal.pone.0056420. Epub 2013 Feb 7.
AHNAK/Desmoyokin is a giant protein which has been recently linked to reorganization of the actin cytoskeleton, cellular migration and invasion. Here, we investigated the role of AHNAK in the pathophysiology of larynx carcinoma-one of the major subtypes of head and neck cancer. To this end, we analysed AHNAK expression in tumor tissues from 83 larynx carcinoma patients in relation to overall survival. We found that tumoral AHNAK overexpression significantly associated with poor survival of these patients both in univariate and multivariate analysis. In further studies, we combined the prognostic value of AHNAK with selected markers of inflammation, such as macrophage migration inhibitory factor (MIF) and tumor-infiltrating neutrophils (CD66b-positive cells). Both MIF and neutrophils have been linked to enhanced tumoral migration and poor clinical outcome in patients with orohypopharynx carcinoma-another major subtype of head and neck cancer. Interestingly, we found that synchronous high levels of AHNAK and MIF or AHNAK and neutrophils, respectively, were stronger predictors of poor survival than AHNAK alone. Synchronous high levels of all three markers were the strongest predictors of poor survival in our patient cohort. Taken together, our findings propose novel strategies for an accurate prognosis in larynx carcinoma and suggest potential mechanisms of inflammation-mediated tumor progression.
AHNAK/Desmoyokin 是一种巨大的蛋白质，最近与肌动蛋白细胞骨架的重组、细胞迁移和侵袭有关。在这里，我们研究了 AHNAK 在喉癌——头颈部癌症的主要亚型之一——的病理生理学中的作用。为此，我们分析了 83 例喉癌患者肿瘤组织中的 AHNAK 表达与总生存率的关系。我们发现，肿瘤中 AHNAK 的过度表达与这些患者的不良预后显著相关，无论是在单因素还是多因素分析中。在进一步的研究中，我们将 AHNAK 的预后价值与炎症的选定标志物（如巨噬细胞移动抑制因子（MIF）和肿瘤浸润性中性粒细胞（CD66b 阳性细胞））相结合。MIF 和中性粒细胞都与口咽癌（另一种头颈部癌症的主要亚型）患者的肿瘤迁移增强和不良临床结果有关。有趣的是，我们发现同时高水平的 AHNAK 和 MIF 或 AHNAK 和中性粒细胞分别比单独的 AHNAK 更能预测不良预后。在我们的患者队列中，这三种标志物同时高水平是不良预后的最强预测因素。总之，我们的研究结果为喉癌的准确预后提供了新的策略，并提示了炎症介导的肿瘤进展的潜在机制。
