Department of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
Oral Oncol. 2013 Aug;49(8):802-7. doi: 10.1016/j.oraloncology.2013.05.006. Epub 2013 Jun 12.
The aim of this cohort study was to examine the role of chemokine (C-X-C motif) ligand 9 (CXCL9) on oral cavity squamous cell carcinoma (OSCC).
Sera from 181 OSCC patients, 231 healthy individuals, and 50 OSCC tumor samples were enrolled. CXCL9 expression in tissue samples was analyzed by quantitative real-time PCR and immunohistochemistry. CXCL9 serum concentrations were measured by enzyme-linked immunosorbent assay. Effects of CXCL9 on OSCC cell function were investigated by cell proliferation assays, trans-well migration/invasion assays, and RNA interference.
CXCL9 expression was significantly higher than for normal epithelium in the tissue samples. CXCL9 serum concentrations were also significantly higher in OSCC patients compared to those in healthy individuals. Serum CXCL9 levels were significantly higher in OSCC patients with higher pT status, pathological overall stages, tumor depths, and positive bone invasion (P = 0.033, 0.004, 0.041, and 0.002, respectively). Moreover, OSCC patients with higher CXCL9 levels (> 209 pg/mL, median level) before treatment had worse prognoses for overall survival and disease-specific survival (P = 0.0006 and 0.0009, respectively). Multivariate logistic regression analyses also indicated that higher CXCL9 serum levels were an independent prognostic factor for overall survival and disease-free survival (P = 0.003 and 0.004, respectively). The in vitro suppression of CXCL9 expression in SCC25 cells using specific interfering RNAs attenuated cell proliferation, migration and invasiveness.
Our study demonstrated that CXCL9 is associated with tumor burden and aggressiveness of OSCC tumors and serum level of this ligand may be useful as a prognostic indicator.
本队列研究旨在探讨趋化因子（C-X-C 基序）配体 9（CXCL9）在口腔鳞状细胞癌（OSCC）中的作用。
纳入了 181 例 OSCC 患者、231 例健康个体和 50 例 OSCC 肿瘤样本的血清。通过定量实时 PCR 和免疫组织化学分析组织样本中的 CXCL9 表达。通过酶联免疫吸附试验测量 CXCL9 血清浓度。通过细胞增殖测定、Transwell 迁移/侵袭测定和 RNA 干扰研究 CXCL9 对 OSCC 细胞功能的影响。
组织样本中 CXCL9 的表达明显高于正常上皮细胞。与健康个体相比，OSCC 患者的血清 CXCL9 浓度也显著升高。在 pT 状态较高、病理总分期较高、肿瘤深度较高和阳性骨侵犯的 OSCC 患者中，血清 CXCL9 水平显著升高（P=0.033、0.004、0.041 和 0.002）。此外，治疗前 CXCL9 水平较高（>209pg/mL，中位数水平）的 OSCC 患者总生存率和疾病特异性生存率较差（P=0.0006 和 0.0009）。多变量逻辑回归分析还表明，较高的 CXCL9 血清水平是总生存率和无病生存率的独立预后因素（P=0.003 和 0.004）。使用特异性干扰 RNA 抑制 SCC25 细胞中的 CXCL9 表达可减弱细胞增殖、迁移和侵袭能力。
本研究表明，CXCL9 与 OSCC 肿瘤的肿瘤负荷和侵袭性相关，该配体的血清水平可能作为一种预后指标有用。
