Use of NRP1, a novel biomarker, along with VEGF-C, VEGFR-3, CCR7 and SEMA3E, to predict lymph node metastasis in squamous cell carcinoma of the tongue.
Use of NRP1, a novel biomarker, along with VEGF-C, VEGFR-3, CCR7 and SEMA3E, to predict lymph node metastasis in squamous cell carcinoma of the tongue.
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DOI：
10.3892/or.2016.5116
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发表时间：
2016-11
期刊：
影响因子：
4.2
通讯作者：
Kogo M
中科院分区：
文献类型：
--
作者：
Al-Shareef H;Hiraoka SI;Tanaka N;Shogen Y;Lee AD;Bakhshishayan S;Kogo M
淋巴结转移是影响口腔癌预后的重要因素。抑制这些转移机制中的生长因子和受体可以显著减少LN转移，提高口腔癌患者治疗后的生存率。因此，本研究旨在评估以下生长因子和受体在舌鳞状细胞癌（SCC）中的表达水平：与细胞表面酪氨酸激酶受体VEGF受体3（VEGFR-3）结合的血管内皮生长因子（VEGF）-C和VEGF-D、C-C基序趋化因子受体7（CCR 7）、神经纤毛蛋白（NRP）1和NRP 2、C-C基序趋化因子受体3（CCR 7）、C-C基序趋化因子受体4（CCR 7）、CCR 7基序趋化因子4（CCR 7）、CCR 7基序趋和semaphorin 3E（SEMA 3E）。此外，我们评估了微血管密度（MVD）和淋巴管密度（LVD），以证明这些因素与区域LN转移之间的相关性，就临床病理特征而言。最后，我们分析了这些蛋白质与总生存期或无病生存期之间的相关性，以证明其预后价值。单因素分析显示，LN转移与SCC细胞中VEGF-C、VEGFR-3、CCR 7、NRP 1和SEMA 3E的表达水平以及LVD显著相关。与此相反，多变量分析发现LN转移和NRP 1表达之间的关联，以及LN转移和LVD之间的关联;然而，没有发现LN转移和其他蛋白质的表达水平之间的相关性。VEGF-C、VEGFR-3、NRP 1和SEMA 3E的表达水平以及LVD与无病生存期相关。这些结果表明，LN转移与SCC的生存率低。本研究提示NRP 1表达和LVD可能是预测舌鳞癌LN转移风险的独立因素，而VEGF-C、VEGFR-3、CCR 7和SEMA 3E的表达是非独立预测因素。
Lymph node (LN) metastasis has been suggested as a major prognostic factor for oral cancer. Knockdown of the growth factors and receptors involved in these metastatic mechanisms could significantly reduce LN metastasis and improve the survival of oral cancer patients after treatment. The present study, therefore, aimed to evaluate the expression levels of the following growth factors and receptors in squamous cell carcinoma (SCC) of the tongue: the vascular endothelial growth factor (VEGF)-C and VEGF-D, which bind to the cell surface tyrosine kinase receptor VEGF receptor-3 (VEGFR-3); C-C motif chemokine receptor 7 (CCR7); neuropilin (NRP)1 and NRP2; and semaphorin 3E (SEMA3E). Furthermore, we assessed microvessel density (MVD) and lymphatic vessel density (LVD) to demonstrate the correlation between these factors and regional LN metastasis, with respect to the clinicopathological features. Finally, we analyzed the correlation between these proteins and overall or disease-free survival, in order to demonstrate their prognostic value. Univariate analysis revealed a significant association between LN metastasis and the expression levels of VEGF-C, VEGFR-3, CCR7, NRP1, and SEMA3E, as well as LVD, in SCC cells. In contrast, multivariate analysis identified associations between LN metastasis and NRP1 expression, as well as between LN metastasis and LVD; however, no correlation was found between LN metastasis and the expression levels of the other proteins. The expression levels of VEGF-C, VEGFR-3, NRP1, and SEMA3E, as well as LVD, were correlated with disease-free survival time. These results indicate that LN metastasis is associated with poor survival in SCC. This study suggests that NRP1 expression and LVD are independent factors that are likely to predict the risk of LN metastasis in SCC of the tongue, whereas the expression of VEGF-C, VEGFR-3, CCR7, and SEMA3E are non-independent predictive factors.
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影响因子：
--
作者：
Bender RJ;Mac Gabhann F
通讯作者：
Mac Gabhann F
影响因子：
4.7
作者：
Chaudary, Naz;Milosevic, Michael;Hill, Richard P.
通讯作者：
Hill, Richard P.
影响因子：
4.8
作者：
George, ML;Tutton, MG;Swift, RI
通讯作者：
Swift, RI
影响因子：
15.9
作者：
Casazza, Andrea;Finisguerra, Veronica;Tamagnone, Luca
通讯作者：
Tamagnone, Luca
影响因子：
11.5
作者：
Miyata, Y;Kanda, S;Kanetake, H
通讯作者：
Kanetake, H