Analysis of Death Receptor 5 and Caspase-8 Expression in Primary and Metastatic Head and Neck Squamous Cell Carcinoma and Their Prognostic Impact
Analysis of Death Receptor 5 and Caspase-8 Expression in Primary and Metastatic Head and Neck Squamous Cell Carcinoma and Their Prognostic Impact
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DOI：
10.1371/journal.pone.0012178
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发表时间：
2010-08-16
期刊：
影响因子：
3.7
通讯作者：
Sun, Shi-Yong
中科院分区：
文献类型：
--
作者：
Elrod, Heath A.;Fan, Songqing;Sun, Shi-Yong
死亡受体5（DR 5）和半胱天冬酶-8是外源性凋亡途径中的主要成分。这些蛋白在头颈部鳞状细胞癌（HNSCC）转移过程中的表达变化及其对预后的影响尚未见报道。本研究通过免疫组织化学（IHC）分析了原发性和转移性HNSCC中DR 5和caspase-8的表达及其对患者生存的影响。本研究中的肿瘤样品包括100个没有转移证据的原发性HNSCC、100个具有淋巴结转移（LNM）的原发性HNSCC和100个匹配的LNM。IHC分析显示，与没有转移证据的原发性肿瘤相比，在具有转移的原发性肿瘤及其匹配的LNM中DR 5表达显著丢失或下调。在caspase-8表达中观察到类似的趋势，尽管其没有统计学显著性。与中分化和高分化肿瘤相比，低分化肿瘤中caspase-8和DR 5表达的下调显著相关。单因素分析显示，在无转移的HNSCC中，caspase-8的高表达与较好的无病生存期和总生存期显著相关。然而，在伴有LNM的HNSCC中，caspase-8的高表达与较差的无病生存期和总生存期显著相关。当我们组合DR 5和caspase-8时也产生了类似的结果。综上所述，我们认为DR 5和caspase-8都参与了HNSCC转移的调节。我们的研究结果保证了对caspase-8在癌症发展中的双重作用的进一步研究。
Death receptor 5 (DR5) and caspase-8 are major components in the extrinsic apoptotic pathway. The alterations of the expression of these proteins during the metastasis of head and neck squamous cell carcinoma (HNSCC) and their prognostic impact have not been reported. The present study analyzes the expression of DR5 and caspase-8 by immunohistochemistry (IHC) in primary and metastatic HNSCCs and their impact on patient survival. Tumor samples in this study included 100 primary HNSCC with no evidence of metastasis, 100 primary HNSCC with lymph node metastasis (LNM) and 100 matching LNM. IHC analysis revealed a significant loss or downregulation of DR5 expression in primary tumors with metastasis and their matching LNM compared to primary tumors with no evidence of metastasis. A similar trend was observed in caspase-8 expression although it was not statistically significant. Downregulation of caspase-8 and DR5 expression was significantly correlated with poorly differentiated tumors compared to moderately and well differentiated tumors. Univariate analysis indicates that, in HNSCC with no metastasis, higher expression of caspase-8 significantly correlated with better disease-free survival and overall survival. However, in HNSCC with LNM, higher caspase-8 expression significantly correlated with poorer disease-free survival and overall survival. Similar results were also generated when we combined both DR5 and caspase-8. Taken together, we suggest that both DR5 and caspase-8 are involved in regulation of HNSCC metastasis. Our findings warrant further investigation on the dual role of caspase-8 in cancer development.