Endoplasmic reticulum ribosome-binding protein 1, RRBP1, promotes progression of colorectal cancer and predicts an unfavourable prognosis.
Endoplasmic reticulum ribosome-binding protein 1, RRBP1, promotes progression of colorectal cancer and predicts an unfavourable prognosis.
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内质网核糖体结合蛋白 1 (RRBP1) 促进结直肠癌进展并预测不良预后
DOI：
10.1038/bjc.2015.260
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发表时间：
2015-09-01
影响因子：
8.8
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Pan Y;Cao F;Guo A;Chang W;Chen X;Ma W;Gao X;Guo S;Fu C;Zhu J
背景：核糖体结合蛋白1（Ribosome-binding protein 1，RRBP 1）参与了未折叠蛋白反应的调控，而未折叠蛋白反应几乎涉及癌症发生发展的各个方面。本研究旨在探讨RRBP 1在结直肠癌（CRC）进展和预后中的意义。免疫组化（IHC）检测结直肠组织中RRBP 1的表达。在成对的癌旁组织中评估RRBP 1表达与CRC发生的相关性。影响预后的因素采用单变量和多变量考克斯分析的训练验证设计进行评估。结果：RRBP 1在大肠癌细胞中异常过表达，RRBP 1在大肠癌细胞中的表达与大肠癌的侵袭性有关。在多变量考克斯分析中，与低RRBP 1患者相比，高RRBP 1患者在训练队列（风险比（HR），2.423; 95%置信区间（CI），1.531-3.835）和验证队列（HR，3.749; 95% CI，2.166-6.448）中的疾病特异性生存期较短。在验证队列中，高RRBP 1独立预测较短的无病生存期（HR，4.821; 95%CI，3.220-7.218）。RRBP 1敲低降低了体外CRC细胞的侵袭性并抑制了体内CRC异种移植物的生长。结论：RRBP 1高表达促进了CRC进展并预测了不利的术后预后。主要结直肠癌（CRC）是世界上第三大常见癌症，全球每年有超过一百万新诊断的患者（Cunningham et al，2010）。其中，约14-25%被诊断为远处转移（Jemal et al，2011），并且通常预后不良。手术切除对局部和区域CRC患者尤其有效（Jemal et al，2011）。然而，这些患者中有30-50%在手术后会发生局部复发和异时性转移，其中许多人会死于复发（Schmoll et al，2012）。术后化疗对那些更容易复发的患者有益。然而，由于化疗的许多副作用，对可能不会复发的患者进行过度治疗往往是有害的（Iinuma et al，2011; Yothers et al，2013）。因此，在早期发现患者并制定一定的选择标准，如用于CRC预后分类的生物标志物，是非常重要的。
Background:Ribosome-binding protein 1 (RRBP1) has been implicated in the regulation of unfolded protein response, which is involved in almost every aspect of cancer development. We aimed to explore the significance of RRBP1 in the progression and prognosis of colorectal cancer (CRC).Methods:The study population consisted of 856 patients with stage I–III CRC from two hospitals. RRBP1 expression was examined by immunohistochemisty (IHC) in colorectal tissues. The correlation of RRBP1 expression and CRC occurrence was assessed in paired cancer-adjacent tissues. Factors contributing to prognosis were evaluated in a training-validation design with univariate and multivariate Cox analysis. Colorectal cancer aggressiveness caused by RRBP1 knockdown or overexpression was evaluated in CRC cells.Results:RRBP1 was aberrantly overexpressed in CRC. Compared with low-RRBP1 patients, high-RRBP1 patients had shorter disease-specific survival in the training (hazard ratio (HR), 2.423; 95% confidence interval (CI), 1.531–3.835) and validation cohorts (HR, 3.749; 95% CI, 2.166–6.448) in multivariate Cox analysis. High-RRBP1 independently predicted a shorter disease-free survival (HR, 4.821; 95% CI, 3.220–7.218) in the validation cohort. RRBP1 knockdown reduced the aggressiveness of CRC cells in vitro and inhibited the growth of CRC xenografts in vivo.Conclusions:High RRBP1 expression facilitates CRC progression and predicts an unfavourable post-operative prognosis.MainColorectal cancer (CRC) is the third most common cancer in the world, with more than one million newly diagnosed patients annually worldwide (Cunningham et al, 2010). Of those, approximately 14–25% are diagnosed with distant metastasis (Jemal et al, 2011), and usually have a poor prognosis. Surgical resection is especially effective for patients with localised and regional CRC (Jemal et al, 2011). However, 30–50% of those patients after surgery will develop local recurrence and metachronous metastases, and many of whom will die from the recurrence (Schmoll et al, 2012). Post-operative chemotherapy is beneficial to those patients who are more likely to develop recurrence. However, overtreatment of patients who may not develop recurrence tends to be harmful, owing to many side effects of chemotherapy (Iinuma et al, 2011; Yothers et al, 2013). Therefore, it is of great importance to find patients in the early stage and develop certain selection criteria, such as biomarkers for prognostic classification of CRC.