Prognostic impact of Fas-associated death domain, a key component in death receptor signaling, is dependent on the presence of lymph node metastasis in head and neck squamous cell carcinoma
Prognostic impact of Fas-associated death domain, a key component in death receptor signaling, is dependent on the presence of lymph node metastasis in head and neck squamous cell carcinoma
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DOI：
10.4161/cbt.23636
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发表时间：
2013-04-01
影响因子：
3.6
通讯作者：
Sun, Shi-Yong
中科院分区：
文献类型：
--
作者：
Fan, Songqing;Mueller, Susan;Sun, Shi-Yong
FAS相关死亡结构域（FADD）是连接死亡受体（如：例如，在一个实施例中，死亡受体5; DR 5）与胱天蛋白酶-8结合，从而在细胞凋亡过程中形成死亡诱导信号复合物。FADD在头颈部鳞状细胞癌（HNSCC）中的表达和预后影响尚未得到很好的研究。本研究的重点是检测FADD的表达，并分析其在原发性和转移性HNSCC的预后影响。我们发现与无淋巴结转移的原发性肿瘤相比，有淋巴结转移的原发性肿瘤中FADD表达显著增加。这种增加在匹配的LNM组织中显著较少。单变量和多变量分析均表明，较低的FADD表达与具有LNM的HNSCC患者的较好的无病生存期和总生存期显著相关，尽管FADD表达并不显著影响没有LNM的HNSCC患者的生存期。当结合DR 5或caspase-8表达时，低FADD和DR 5表达或低FADD和caspase-8表达的LNM患者的预后显著优于高FADD和DR 5表达或高FADD和caspase-8表达的LNM患者。然而，在没有LNM的HNSCC患者中，与FADD和caspase-8的高表达相比，FADD和caspase-8的低表达与更差的总生存率显著相关。因此，我们认为FADD单独或与DR 5和caspase-8共同参与了HNSCC的转移过程。
FAS-associated death domain (FADD) is a key adaptor protein that bridges a death receptor (e. g., death receptor 5; DR5) to caspase-8 to form the death-inducing signaling complex during apoptosis. The expression and prognostic impact of FADD in head and neck squamous cell carcinoma (HNSCC) have not been well studied. This study focuses on detecting FADD expression and analyzing its prognostic impact in primary and metastatic HNSCCs. We found a significant increase in FADD expression in primary tumors with lymph node metastasis (LNM) in comparison with primary tumors with no LNM. This increase was significantly less in the matched LNM tissues. Both univariate and multivariable analyses indicated that lower FADD expression was significantly associated with better disease-free survival and overall survival in HNSCC patients with LNM although FADD expression did not significantly affect survival of HNSCC patients without LNM. When combined with DR5 or caspase-8 expression, patients with LNM expressing both low FADD and DR5 or both low FADD and caspase-8 had significantly better prognosis than those expressing both high FADD and DR5 or both high FADD and caspase-8. However, the expression of both low FADD and caspase-8 was significantly linked to worse overall survival compared with both high FADD and caspase-8 expression in HNSCC patients without LNM. Hence, we suggest that FADD alone or together with DR5 and caspase-8 participates in metastatic process of HNSCC.