Correlation of TNFAIP8 overexpression with the proliferation, metastasis, and disease-free survival in endometrial cancer
Correlation of TNFAIP8 overexpression with the proliferation, metastasis, and disease-free survival in endometrial cancer
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DOI：
10.1007/s13277-014-1770-y
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发表时间：
2014-06-01
期刊：
影响因子：
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通讯作者：
Lou, Ge
中科院分区：
文献类型：
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作者：
Liu, Tianbo;Gao, Hongyu;Lou, Ge
肿瘤坏死因子α诱导蛋白8（TNFAIP 8）是一种凋亡调节因子，被证明在恶性肿瘤的增殖、侵袭、转移和进展中具有重要功能。在这项研究中，我们调查了TNFAIP 8过度表达在子宫内膜癌（EC）的临床作用，并确定TNFAIP 8与增殖抗原Ki-67和转移相关基因基质金属肽酶9（MMP 9）在225例肿瘤标本中的关系，通过免疫组织化学和蛋白质印迹，以阐明更多的信息TNFAIP 8蛋白在EC的发病机制方面的作用。TNFAIP 8的过表达与国际妇产科联合会（IFG）分期（P < 0.001）、组织学分级（P = 0.017）、深肌层浸润（P = 0.030）、淋巴管浸润（P = 0.011）、淋巴结转移（P < 0.001）和复发等临床病理因素有关。此外，TNFAIP 8过表达与MMP 9和Ki-67表达在EC的进展中强烈相关。TNFAIP 8（P < 0.001）和Ki-67（P = 0.007和P = 0.008）高表达的患者总生存率和无病生存率（DFS）较差。MMP 9过表达对生存率无影响（P > 0.05）。多因素考克斯回归分析显示TNFAIP 8（P = 0.029）和淋巴结转移（P = 0.022）是食管癌患者DFS的独立影响因素。提示TNFAIP 8可作为食管癌复发的预后指标，其促进食管癌增殖和转移的作用可能与其介导Ki-67和MMP 9有关。
Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is an apoptosis regulator proven to have an important function in the proliferation, invasion, metastasis, and progression of malignancies. In this study, we investigated the clinical role of TNFAIP8 overexpression in endometrial cancer (EC) and determined the relationship of TNFAIP8 with the proliferative antigen Ki-67 and metastasis-related gene matrix metallopeptidase 9 (MMP9) in 225 tumor specimens by immunohistochemistry and western blot, in order to elucidate more information on the role of TNFAIP8 protein with regard to the pathogenesis of EC. An association was observed between TNFAIP8 overexpression and clinicopathologic factors, such as advanced International Federation of Gynecology and Obstetrics stage (P < 0.001), higher histologic grade (P = 0.017), deep myometrial invasion (P = 0.030), lymphovascular space invasion (P = 0.011), lymph node metastasis (P < 0.001), and recurrence. Furthermore, TNFAIP8 overexpression was strongly correlated with MMP9 and Ki-67 expression in the progression of ECs. Patients with high expression of TNFAIP8 (P < 0.001 for both) and Ki-67 (P = 0.007 and P = 0.008) had poor overall survival and disease-free survival (DFS) rates. MMP9 overexpression did not affect survival outcomes (P > 0.05). Multivariate Cox regression analysis revealed that TNFAIP8 (P = 0.029) and lymph node metastasis (P = 0.022) were independent factors of DFS in patients with EC. These findings suggested that TNFAIP8 may be used as a prognostic marker for the recurrence of EC, and its promotion of the proliferation and metastasis in EC may be due to its mediation of Ki-67 and MMP9.