Prognostic significance of Jab1 expression in laryngeal squamous cell carcinomas.
Prognostic significance of Jab1 expression in laryngeal squamous cell carcinomas.
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发表时间：
2005
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通讯作者：
Youyi Dong;L. Sui;Yasuo Watanabe;F. Yamaguchi;N. Hatano;M. Tokuda
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作者：
Youyi Dong;L. Sui;Yasuo Watanabe;F. Yamaguchi;N. Hatano;M. Tokuda
Jun活化结构域结合蛋白1 （Jun activation domain binding protein 1, Jab1）是AP1转录因子的辅助激活因子，通过降解p27kip1蛋白促进肿瘤进展。本研究旨在探讨Jab1表达是否与p27kip1水平及细胞增殖相关，以及Jab1表达是否与喉鳞癌（LSCC）的临床病理变量及预后相关。实验设计对HEp-2细胞和102例LSCCs进行免疫组化和/或Western blot分析。结果在HEp-2细胞和LSCCs中，Jab1表达与p27kip1表达呈负相关，与细胞增殖呈正相关。在51%的LSCCs中检测到Jab1过表达，并且与不利的临床病理变量显著相关。生存分析显示，Jab1过表达与短期无病生存和总生存显著相关（P = 0.0036和P = 0.0001）。当Jab1和p27kip1联合使用时，Jab1(+)/p27kip1（-）患者的无病生存期和总生存期较差（P分别为0.0008和P < 0.0001）。当Jab1表达和淋巴结状态相结合时，Jab1(+)/淋巴结（+）患者的无病生存率和总生存率比其他患者差（P < 0.0001和P < 0.0001）。此外，Jab1(+)/p27kip1(-)/淋巴结（+）表型患者的无病生存率和总生存率最差（P < 0.0001和P < 0.0001）。多因素分析显示，Jab1蛋白是总体生存的独立预后指标。结论：这些研究结果表明，Jab1蛋白可能有助于肿瘤的进展，并代表了LSCCs的一种新的预后指标。
PURPOSE Jun activation domain-binding protein 1 (Jab1) is known as a coactivator of AP1 transcription factor, which contributes to tumor progression by degrading the p27kip1 protein. The purpose of this study is to investigate whether Jab1 expression is correlated with p27kip1 level and cell proliferation, as well as whether Jab1 expression is associated with clinicopathologic variables and prognosis of laryngeal squamous cell carcinoma (LSCC). EXPERIMENTAL DESIGN Immunohistochemical and/or Western blot analysis was done in HEp-2 cells and 102 cases of LSCCs. RESULTS Jab1 expression was negatively associated with p27kip1 expression and was positively associated with cell proliferation both in HEp-2 cells and LSCCs. Jab1 overexpression was detected in 51% LSCCs and was significantly associated with unfavorable clinicopathologic variables. Survival analysis revealed that Jab1 overexpression is significantly associated with short disease-free and overall survival (P = 0.0036 and P = 0.0001, respectively). When Jab1 and p27kip1 are combined, patients with Jab1(+)/p27kip1(-) revealed poor disease-free and overall survival (P= 0.0008 and P < 0.0001, respectively). When Jab1 expression and lymph node status are combined, patients with Jab1(+)/lymph node(+) revealed poorer disease-free andoverall survival than others (P < 0.0001 and P < 0.0001, respectively). Furthermore, patients with the phenotype of Jab1(+)/p27kip1(-)/lymph node(+) revealed the worst disease-free and overall survival (P < 0.0001 and P < 0.0001, respectively). Multivariate analysis revealed that Jab1 protein is an independent prognostic indicator for overall survival. CONCLUSIONS These findings suggested that Jab1 protein may contribute to the tumor progression and represent a novel prognostic indicator for LSCCs.