Macher-Goeppinger Stephan, Keith Martina, Hatiboglu Gencay, Hohenfellner Markus, Schirmacher Peter, Roth Wilfried, Tagscherer Katrin E
Institute of Pathology, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany; Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
Transl Oncol. 2017 Dec;10(6):869-875. doi: 10.1016/j.tranon.2017.08.008. Epub 2017 Sep 15.
BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein 3) is a BH3-only protein that regulates apoptosis and autophagy. BNIP3 plays also an important role in hypoxia-induced cell response and is regulated by HIF1. Here, we studied a possible association of BNIP3 expression and the prognosis of patients with renal cell carcinomas (RCCs) and examined the functional relevance of BNIP3 in the regulation of cell survival and apoptosis of renal carcinoma cells. BNIP3 expression was determined by immunohistochemistry in RCC tumor tissue samples of 569 patients using a tissue microarray. Functional characterization of BNIP3 in renal carcinoma cells indicates prosurvival effects. In human RCC tumor samples, high cytoplasmic BNIP3 expression was associated with high-grade RCCs and regional lymph node metastasis. BNIP3 expression correlated negatively with disease-specific survival. Multivariate Cox regression analysis retained BNIP3 expression as an independent prognostic factor in patients without distant metastasis. Together, our studies imply that BNIP3 regulates cell survival in RCCs and its expression is an independent prognostic marker in patients with localized RCCs.
BNIP3（Bcl-2/腺病毒E1B 19 kDa相互作用蛋白3）是一种仅含BH3结构域的蛋白，可调节细胞凋亡和自噬。BNIP3在缺氧诱导的细胞反应中也发挥重要作用，并受缺氧诱导因子1（HIF1）调控。在此，我们研究了BNIP3表达与肾细胞癌（RCC）患者预后之间可能存在的关联，并探讨了BNIP3在调控肾癌细胞存活和凋亡中的功能相关性。采用组织芯片，通过免疫组化法检测了569例患者RCC肿瘤组织样本中的BNIP3表达。肾癌细胞中BNIP3的功能特性表明其具有促生存作用。在人RCC肿瘤样本中，高细胞质BNIP3表达与高级别RCC及区域淋巴结转移相关。BNIP3表达与疾病特异性生存率呈负相关。多变量Cox回归分析显示，BNIP3表达是无远处转移患者的独立预后因素。总之，我们的研究表明，BNIP3调节RCC中的细胞存活，其表达是局限性RCC患者的独立预后标志物。
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