Ephrin-B2 overexpression predicts for poor prognosis and response to therapy in solid tumors.
Ephrin-B2 overexpression predicts for poor prognosis and response to therapy in solid tumors.
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DOI：
10.1002/mc.22574
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发表时间：
2017-03
影响因子：
4.6
通讯作者：
Karam SD
中科院分区：
文献类型：
--
作者：
Oweida A;Bhatia S;Hirsch K;Calame D;Griego A;Keysar S;Pitts T;Sharma J;Eckhardt G;Jimeno A;Wang XJ;Parkash G;Califano J;Karam SD
肾上腺素B2在肿瘤细胞上有不同的表达，其阻断已被证明在胰腺癌、结直肠癌、肺和头颈部鳞状细胞癌的动物模型中抑制血管生成。然而，在癌症患者中表达ewitinB2的意义仍然难以捉摸。在这项研究中，我们分析了癌症基因组图谱(TCGA)中ewitinB2的表达。我们报道了EFNB2在头颈部鳞状细胞癌(HNSCC，n=519)、胰腺癌(n=186)和膀胱尿路上皮癌(n=410)中的表达与总生存率和无瘤生存率之间的显著相关性。在HNSCC患者中，EFNB2mRNA的高表达与肿瘤HPV阴性、口腔位置、饮酒、较高的TP53突变和EGFR扩增相关。EPhinB2的过度表达也与化疗和放射治疗的不良反应有关。阻断eparinB2的治疗潜力在HNSCC患者来源的肿瘤移植瘤中得到验证，并显示出在存活率和肿瘤生长延迟方面的显著改善。我们的数据表明，ewitinB2的过度表达可以作为判断患者预后和治疗反应的关键生物标志物。这些结果将指导未来临床试验的设计，探索在癌症患者中抑制EPhinB2的作用。
Ephrin B2 is variably expressed on tumor cells and its blockade has been shown to inhibit angiogenesis in animal models of pancreatic, colorectal, lung and head, and neck squamous cell carcinomas. However, the implications of ephrinB2 expression in cancer patients have remained elusive. In this study, we analyzed the cancer genome atlas (TCGA) for ephrinB2 expression. We report significant correlations between EFNB2 expression, overall survival and disease-free survival in head and neck squamous cell carcinoma (HNSCC, n = 519), pancreatic adenocarcinoma (n = 186), and bladder urothelial carcinoma (n = 410). In HNSCC patients, high-EFNB2 mRNA expression was associated with tumor HPV negativity, oral cavity location, alcohol intake, higher TP53 mutation, and EGFR amplification. EphrinB2 overexpression also correlated with worse response to chemotherapy and radiotherapy. The therapeutic potential of blocking ephrinB2 was validated in HNSCC patient-derived tumor xenografts and showed significant improvement in survival and tumor growth delay. Our data shows that ephrinB2 overexpression can serve as a critical biomarker for patient prognosis and response to therapy. These results should guide design of future clinical trials exploring EphrinB2 inhibition in cancer patients.
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影响因子：
16.6
作者：
Zhang, Gu;Brady, John;Liang, Wei-Ching;Wu, Yan;Henkemeyer, Mark;Yan, Minhong
通讯作者：
Yan, Minhong
影响因子：
78.5
作者：
Pasquale, Elena B.
通讯作者：
Pasquale, Elena B.
影响因子：
50.5
作者：
Alam, S. M.;Fujimoto, J.;Tamaya, T.
通讯作者：
Tamaya, T.
影响因子：
16.6
作者：
Thakar, Sonal;Chenaux, George;Henkemeyer, Mark
通讯作者：
Henkemeyer, Mark
影响因子：
2.7
作者：
Cowan, CA;Yokoyama, N;Henkemeyer, M
通讯作者：
Henkemeyer, M