Alteration status and prognostic value of MET in head and neck squamous cell carcinoma.
Alteration status and prognostic value of MET in head and neck squamous cell carcinoma.
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DOI：
10.7150/jca.16686
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发表时间：
2016
影响因子：
3.9
通讯作者：
Yoon SO
中科院分区：
文献类型：
--
作者：
Cho YA;Kim EK;Heo SJ;Cho BC;Kim HR;Chung JM;Yoon SO
MET通路在各种癌症中起着关键作用，其抑制代表了潜在的治疗靶点。然而，需要适当的生物标志物来帮助选择将从MET抑制治疗中获益的患者。在此，我们对接受标准手术切除和辅助放化疗的头颈部鳞状细胞癌（HNSCC）患者（n = 396）的MET拷贝数改变状态和c-Met表达的预后意义进行了强有力的验证性评估。对手术切除的HNSCC样本进行c-Met表达的免疫组织化学和H评分分析以及MET扩增和拷贝数增加的银原位杂交分析。c-Met表达各不相同，平均和中位H评分（量表：0-300量表）分别为61.2和60.0。在喉和口腔SCC中分别观察到最低和最高表达水平。在16.9%的病例（67/339）中观察到MET拷贝数增加，并与c-Met蛋白表达相关。根据MET获得状态确定的高c-Met表达与较差的总生存率相关，特别是在完全切除的病例中。总之，我们的稳健分析显示，c-Met在HNSCCs中的表达根据解剖部位而变化，与MET拷贝数增加相关，并且与不良预后相关。这种基于MET获得状态的c-Met表达分析方法似乎可以在抗MET治疗决策的背景下适当预测高风险HNSCC患者。
The MET pathway plays a key role in various cancers, and its inhibition represents a potential treatment target. However, appropriate biomarkers are needed to facilitate the selection of patients who would benefit from MET inhibiting therapy. We herein conducted a robust confirmatory evaluation of the MET copy number alteration status and prognostic significance of c-Met expression in a large series of patients (n = 396) who underwent standard surgical resection and adjuvant chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC). Surgically resected HNSCC samples were subjected to immunohistochemical and H-score analysis of c-Met expression and silver in situ hybridization analysis of MET amplification and copy number gains. c-Met expression varied, with mean and median H-scores (scale: 0-300 scale) of 61.2 and 60.0, respectively. The lowest and highest expression levels were observed in SCC of the larynx and oral cavity, respectively. MET copy number gains were observed in 16.9% of cases (67/339) and were associated with c-Met protein expression. High c-Met expression, determined according to MET gain status, was associated with an inferior overall survival rate, especially among completely resected cases. In conclusion, our robust analysis revealed that c-Met expression in HNSCCs varied according to anatomical site, correlated with MET copy number gains, and was associated with poor prognosis. This c-Met expression analysis method, which is based on the MET gain status, appears to appropriately predict high-risk HNSCC patients in the context of anti-MET therapeutic decisions.
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MET蛋白过表达和基因扩增在局部晚期鼻咽癌中的预后价值
影响因子：
--
作者：
Li Y;Li W;He Q;Xu Y;Ren X;Tang X;Wen X;Yang X;Sun Y;Zeng J;Yun J;Liu N;Ma J
通讯作者：
Ma J
影响因子：
3.3
作者：
Kwon, Mi Jung;Kim, Dong Hoon;Nam, Eun Sook
通讯作者：
Nam, Eun Sook
影响因子：
5.7
作者：
Merlin, Simone;Pietronave, Stefano;Prat, Maria
通讯作者：
Prat, Maria
影响因子：
21.3
作者：
Joffre, Carine;Barrow, Rachel;Kermorgant, Stephanie
通讯作者：
Kermorgant, Stephanie
影响因子：
8.8
作者：
Lee, H. E.;Kim, M. A.;Lee, H. S.;Jung, E-J;Yang, H-K;Lee, B. L.;Bang, Y-J;Kim, W. H.
通讯作者：
Kim, W. H.