A novel role for TNFAIP2: its correlation with invasion and metastasis in nasopharyngeal carcinoma
A novel role for TNFAIP2: its correlation with invasion and metastasis in nasopharyngeal carcinoma
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DOI：
10.1038/modpathol.2010.193
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发表时间：
2011-02-01
期刊：
影响因子：
7.5
通讯作者：
Hsueh, Chuen
中科院分区：
文献类型：
--
作者：
Chen, Lih-Chyang;Chen, Chia-Chun;Hsueh, Chuen
肿瘤坏死因子α（TNF α）是一种炎性细胞因子，存在于许多肿瘤的微环境中，已知可促进肿瘤进展。为了研究TNF α是如何调节鼻咽癌的进展和转移的，我们使用了Affytron芯片来鉴定在这种肿瘤中失调的TNF α诱导基因。TNFAIP 2的表达升高，其编码TNF α诱导蛋白2，并且先前不知道与癌症相关，通过TNFAIP 2在鼻咽癌和邻近正常组织中表达的定量RT-PCR发现并证实。免疫组化结果显示TNFAIP 2蛋白在肿瘤细胞中呈高表达。对95例鼻咽癌活检标本的分析显示，TNFAIP 2高表达与高水平的肿瘤内微血管密度（P = 0.005）和低的无远处转移生存率（P = 0.001）显著相关。多因素分析进一步证实TNFAIP 2是鼻咽癌的独立预后因素（P = 0.002）。在体外，发现TNF α处理鼻咽癌HK 1细胞诱导TNFAIP 2表达，并且基于siRNA的TNFAIP 2敲低显著降低鼻咽癌HK 1细胞的迁移和侵袭。这些结果首次共同表明TNFAIP 2是一种细胞迁移促进蛋白，其表达预测远处转移。TNFAIP 2可能作为鼻咽癌独立的预后指标。Modern Pathology（2011）24，175-184; doi：10.1038/modpathol.2010.193; 2010年11月5日在线发表
Tumor necrosis factor alpha (TNF alpha) is an inflammatory cytokine that is present in the microenvironment of many tumors and is known to promote tumor progression. To examine how TNF alpha modulates the progression and metastasis of nasopharyngeal carcinoma, we used Affymetrix chips to identify TNF alpha-inducible genes that are dysregulated in this tumor. Elevated expression of TNFAIP2, which encodes TNF alpha-inducible protein 2 and not previously known to be associated with cancer, was found and confirmed by quantitative RT-PCR of TNFAIP2 expression in nasopharyngeal carcinoma and adjacent normal tissues. Immunohistochemical analysis showed that the TNFAIP2 protein was highly expressed in tumor cells. Analysis of 95 nasopharyngeal carcinoma biopsy specimens revealed that high TNFAIP2 expression was significantly correlated with high-level intratumoral microvessel density (P = 0.005) and low distant metastasis-free survival (P = 0.001). A multivariate analysis further confirmed that TNFAIP2 was an independent prognostic factor for nasopharyngeal carcinoma (P = 0.002). In vitro, TNF alpha treatment of nasopharyngeal carcinoma HK1 cells was found to induce TNFAIP2 expression, and siRNA-based knockdown of TNFAIP2 dramatically reduced the migration and invasion of nasopharyngeal carcinoma HK1 cells. These results collectively suggest for the first time that TNFAIP2 is a cell migration-promoting protein and its expression predicts distant metastasis. Our data suggest that TNFAIP2 may serve as an independent prognostic indicator for nasopharyngeal carcinoma. Modern Pathology (2011) 24, 175-184; doi:10.1038/modpathol.2010.193; published online 5 November 2010