血管生成素-2和血管内皮生长因子受体-3的表达与淋巴管生成和血管生成相关，并影响口腔鳞状细胞癌的生存。

Expression of angiopoietin-2 and vascular endothelial growth factor receptor-3 correlates with lymphangiogenesis and angiogenesis and affects survival of oral squamous cell carcinoma.

作者信息

Li Chao, Fan Jinchuan, Song Xicheng, Zhang Bing, Chen Yu, Li Chunhua, Mi Kun, Ma Hong, Song Yufeng, Tao Xiaofeng, Li Guojun

机构信息

Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu, China ; State Key Laboratory of Oral Diseases in Sichuan University, Sichuan, China.

出版信息

PLoS One. 2013 Sep 11;8(9):e75388. doi: 10.1371/journal.pone.0075388. eCollection 2013.

BACKGROUND

Both Ang-2 and VEGFR-3 are major regulators of angiogenesis and lymphangiogenesis, respectively, and thus may affect prognosis of OSCC. We sought to determine the associations between Ang-2 and VEGFR-3 expression and survival of OSCC.

METHODS

Ang-2 and VEGFR-3 expression was determined immunohistochemically in tumor tissues from 112 patients with OSCC; OSCC-adjacent noncancerous oral tissue from 85 OSCC patients; and normal oral mucosa from 37 cancer-free individuals. A log-rank test and Cox proportional hazard models were used to compare survival among different groups with expression of Ang-2 and VEGFR-3.

RESULTS

Ang-2 and VEGFR-3 expression was upregulated in OSCC compared to nontumor tissue (all P<0.05). High Ang-2 expression positively correlated with microvessel density (MVD) (P<0.01), and high VEGFR-3 expression positively correlated with lymph node metastasis (P<0.01) and lymphatic vessel density (LVD) (P<0.01). The patients with high expression of Ang-2 alone or in combination with VEGFR-3 had a significantly worse survival than in patients with low expression of Ang-2 or any other co-expression status (all P<0.05), respectively. Furthermore, multivariable analysis showed that patients with high expression of Ang-2 alone or in combination with VEGFR-3 had a significantly increased risk of death compared with those with low expression of Ang-2 or any other co-expression status (HR, 2.7, 95% CI, 1.1-6.2 and 5.0, 1.3-15.4, respectively).

CONCLUSIONS

These results suggest that increased expression in tumors of Ang-2 may individually, or in combination with VEGFR-3, predict poor prognosis of OSCC.

背景

血管生成素-2（Ang-2）和血管内皮生长因子受体-3（VEGFR-3）分别是血管生成和淋巴管生成的主要调节因子，因此可能影响口腔鳞状细胞癌（OSCC）的预后。我们试图确定Ang-2和VEGFR-3表达与OSCC患者生存率之间的关联。

方法

采用免疫组织化学方法检测112例OSCC患者肿瘤组织、85例OSCC患者癌旁非癌口腔组织及37例无癌个体正常口腔黏膜中Ang-2和VEGFR-3的表达。采用对数秩检验和Cox比例风险模型比较不同Ang-2和VEGFR-3表达组的生存率。

结果

与非肿瘤组织相比，OSCC中Ang-2和VEGFR-3表达上调（所有P<0.05）。Ang-2高表达与微血管密度（MVD）呈正相关（P<0.01），VEGFR-3高表达与淋巴结转移（P<0.01）和淋巴管密度（LVD）呈正相关（P<0.01）。单独Ang-2高表达或与VEGFR-3联合高表达的患者生存率明显低于Ang-2低表达或其他共表达状态的患者（所有P<0.05）。此外，多变量分析显示，单独Ang-2高表达或与VEGFR-3联合高表达的患者死亡风险明显高于Ang-2低表达或其他共表达状态的患者（风险比分别为2.7，95%可信区间为1.1 - 6.2；5.0，1.3 - 15.4）。