Department of General Surgical Science (Surgery 1), Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan.
Ann Surg Oncol. 2012 Jul;19 Suppl 3:S589-96. doi: 10.1245/s10434-011-2097-1. Epub 2011 Oct 4.
Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is a suppressor of TNF-α mediated apoptosis, and its expression is induced by NF-κB activation. TNFAIP8 expression is significantly increased in various cancer cell lines. A correlation between TNFAIP8 overexpression, cancer progression, and poor prognosis has been described in many reports of human solid cancers.
To clarify the functional and clinical significance of the cancer progression-related gene, TNFAIP8, in esophageal squamous cell carcinoma (ESCC), we used immunohistochemistry to demonstrate TNFAIP8 expression in ESCC. Next, TNFAIP8 expression was depleted by using siRNA to examine the function of TNFAIP8 in the proliferation and apoptosis induction of ESCC cell lines.
We detected correlations between TNFAIP8 expression and TNM stage (P < 0.001), tumor depth (P = 0.002), lymph node metastasis (P = 0.013), distant metastasis (P = 0.001), lymphatic invasion (P < 0.001), and venous invasion (P < 0.001) among the clinicopathological characteristics of ESCC patients, and high TNFAIP8 expression was found in poor survival. TNFAIP8 depletion was significantly associated with apoptosis induction after cisplatin administration and reduced proliferation.
Our results suggest that TNFAIP8 might be an effective therapeutic target for ESCC in the future.
肿瘤坏死因子-α诱导蛋白 8(TNFAIP8)是 TNF-α 介导凋亡的抑制剂,其表达受 NF-κB 激活诱导。TNFAIP8 在各种癌细胞系中的表达显著增加。许多人类实体癌的报告描述了 TNFAIP8 过表达与癌症进展和预后不良之间的相关性。
为了阐明与癌症进展相关基因 TNFAIP8 在食管鳞状细胞癌(ESCC)中的功能和临床意义,我们使用免疫组织化学法检测 ESCC 中 TNFAIP8 的表达。接下来,使用 siRNA 耗尽 TNFAIP8 表达,以检查 TNFAIP8 在 ESCC 细胞系增殖和凋亡诱导中的功能。
我们检测到 TNFAIP8 表达与 ESCC 患者的临床病理特征中的 TNM 分期(P < 0.001)、肿瘤深度(P = 0.002)、淋巴结转移(P = 0.013)、远处转移(P = 0.001)、淋巴侵袭(P < 0.001)和静脉侵袭(P < 0.001)之间存在相关性,并且发现 TNFAIP8 高表达与生存不良相关。TNFAIP8 耗竭与顺铂给药后诱导凋亡和减少增殖显著相关。
我们的结果表明,TNFAIP8 可能是未来 ESCC 的有效治疗靶点。