Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Ann Surg Oncol. 2012 Jul;19 Suppl 3:S500-8. doi: 10.1245/s10434-011-1985-8. Epub 2011 Aug 13.
Overexpression of the receptor tyrosine kinase Axl is implicated in several diseases. The present study was conducted to determine the biologic and clinical significance of Axl in oral squamous cell carcinoma (OSCC).
The expression of Axl was examined in a panel of OSCC cell lines. Activation of Axl by Gas6 treatment and silencing of Axl via Axl shRNA were used to examine the effect of Axl on OSCC cell line. Expression of Axl in cancer tissues were examined by immunohistochemical staining. The associations between Axl expression and clinicopathologic features and prognosis were analyzed.
Varied Axl expression was noted in OSCC cell lines. Compared with control cells, modulated Axl signal affected epithelial-mesenchymal gene expression and cell invasion and migration. The immunoreactivity of Axl was low in normal epithelium, and a progressively increased positive percentage was noted, from normal/hyperplastic epithelium (10.9%) to dysplasia (30.8%) to cancer tissue (54.5%). Axl expression correlated with lymph node status (P = .001) and clinical stage (P = .014) of OSCC. Patients with high expression of Axl showed poor prognosis compared with those with low Axl expression patients (P < .001). In multivariate prognostic analysis according to the Cox proportional hazard regression model, Axl expression remained as an independent prognostic factor (P = .037; CI, 1.042-3.839).
Our data indicated that Axl signal promotes OSCC carcinogenesis and progression. The expression of Axl is a valuable marker for OSCC aggressiveness and clinical outcome.
受体酪氨酸激酶 Axl 的过表达与多种疾病有关。本研究旨在确定 Axl 在口腔鳞状细胞癌（OSCC）中的生物学和临床意义。
在一组 OSCC 细胞系中检查 Axl 的表达。通过 Gas6 处理激活 Axl 并通过 Axl shRNA 沉默 Axl，用于检查 Axl 对 OSCC 细胞系的影响。通过免疫组织化学染色检查 Axl 在癌组织中的表达。分析 Axl 表达与临床病理特征和预后的关系。
在 OSCC 细胞系中观察到不同的 Axl 表达。与对照细胞相比，调节的 Axl 信号影响上皮-间充质基因表达和细胞侵袭和迁移。Axl 的免疫反应性在正常上皮中较低，并且阳性百分比逐渐增加，从正常/增生上皮（10.9%）到发育不良（30.8%）到癌组织（54.5%）。Axl 表达与 OSCC 的淋巴结状态（P =.001）和临床分期（P =.014）相关。与 Axl 低表达患者相比，Axl 高表达的患者预后较差（P <.001）。根据 Cox 比例风险回归模型的多变量预后分析，Axl 表达仍然是独立的预后因素（P =.037；CI，1.042-3.839）。
我们的数据表明 Axl 信号促进了 OSCC 的发生和进展。Axl 的表达是 OSCC 侵袭性和临床结果的有价值的标志物。
