Migita Kazuhiro, Takayama Tomoyoshi, Matsumoto Sohei, Wakatsuki Kohei, Tanaka Tetsuya, Ito Masahiro, Nishiwada Satoshi, Nakajima Yoshiyuki
Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan,
Gastric Cancer. 2014 Oct;17(4):601-9. doi: 10.1007/s10120-013-0318-y. Epub 2013 Nov 29.
RING box protein-1 (RBX1) is an essential component of the E3 ubiquitin ligase Skp1/Cullin/RBX1/F-box protein complex. Although an altered expression of RBX1 has been reported in several human cancers, the role of RBX1 in gastric cancer remains unknown.
We investigated the RBX1 expression in primary gastric cancer tissues from 145 patients by immunohistochemistry, and explored its clinical relevance and prognostic value. Furthermore, the effect of RBX1 expression on cancer cell proliferation was analyzed in vitro using a siRNA silencing technique.
The RBX1 expression was abundant in gastric cancer tissues. There was a significant difference in the expression level of RBX1 in terms of the tumor depth (P = 0.008), presence of distant metastasis (P = 0.016) and venous invasion (P = 0.005). The postoperative overall (P < 0.001) and relapse-free survival (P < 0.001) rates were significantly poorer in patients with RBX1-high tumors than in patients with RBX1-low tumors. There was a significant correlation of the RBX1 status with postoperative hematogenous recurrence (P = 0.013). Importantly, the RBX1 status was identified as an independent prognostic factor for gastric cancer (P = 0.002). Furthermore, RBX1 gene silencing significantly inhibited the proliferation of gastric cancer cells in vitro.
The RBX1 expression has a significant prognostic value in gastric cancer. RBX1 might play an important role in regulating the proliferation of gastric cancer cells and promoting the development of postoperative recurrence. Our data provide a rationale for developing a novel therapy targeting RBX1 for gastric cancer.
RING框蛋白1(RBX1)是E3泛素连接酶Skp1/ Cullin/ RBX1/ F盒蛋白复合物的重要组成部分。虽然已有报道称RBX1在多种人类癌症中表达改变,但其在胃癌中的作用仍不清楚。
我们通过免疫组织化学研究了145例原发性胃癌组织中RBX1的表达情况,并探讨了其临床相关性和预后价值。此外,使用小干扰RNA(siRNA)沉默技术在体外分析了RBX1表达对癌细胞增殖的影响。
RBX1在胃癌组织中大量表达。RBX1的表达水平在肿瘤深度(P = 0.008)、远处转移情况(P = 0.016)和静脉侵犯情况(P = 0.005)方面存在显著差异。RBX1高表达肿瘤患者的术后总生存率(P < 0.001)和无复发生存率(P < 0.001)显著低于RBX1低表达肿瘤患者。RBX1状态与术后血行复发显著相关(P = 0.013)。重要的是,RBX1状态被确定为胃癌的独立预后因素(P = 0.002)。此外,RBX1基因沉默在体外显著抑制了胃癌细胞的增殖。
RBX1表达在胃癌中具有显著的预后价值。RBX1可能在调节胃癌细胞增殖和促进术后复发发展中起重要作用。我们的数据为开发针对RBX1的胃癌新疗法提供了理论依据。