Yoo Peter S, Sullivan Catherine A W, Kiang Sharon, Gao Wenli, Uchio Edward M, Chung Gina G, Cha Charles H
Department of Surgery, Yale University School of Medicine, New Haven, USA.
Ann Surg Oncol. 2009 Jan;16(1):200-7. doi: 10.1245/s10434-008-0209-3. Epub 2008 Nov 14.
The purpose of this study is to characterize the expression of HuR in colorectal carcinoma and determine its correlation with clinical outcome. Differential expression of HuR has been suggested to be of prognostic significance in carcinomas of the ovaries, stomach, and breast. HuR regulates the expression of a variety of proteins critical to carcinogenesis via the pathways of cell-cycle progress, invasion, and metastasis. Increasing evidence suggests that angiogenic pathways are involved. A tissue microarray consisting of tumors from 560 patients with colorectal adenocarcinoma was analyzed for HuR protein expression using a quantitative, automated immunofluorescent microscopy system (AQUA). Clinical data corresponding to each examined specimen collected through an institutional review board (IRB)-approved protocol were analyzed using chi-squared test, Cox regression, and Kaplan-Meier analysis. Median follow-up was 54 months. Along with tumor stage and overall tumor-node-metastasis (TNM) stage, HuR expression was found to be an independent predictor of survival. In patients in the highest quartile of total HuR expression, survival was 22.8 months less than those in the lower quartiles (40.6 versus 63.4 months, p = 0.04). Furthermore, HuR levels correlate positively with expression of vascular endothelial growth factor (VEGF) and CD31, a marker for vascular endothelium. We conclude that expression of high levels of HuR correlates with features of advanced disease and portends poorer survival in patients with colorectal adenocarcinoma. These results further suggest that HuR exerts its tumorigenic effects through VEGF-mediated angiogenesis and may be a novel therapeutic target in colorectal cancer.
本研究的目的是描述HuR在结直肠癌中的表达特征，并确定其与临床结局的相关性。已有研究表明，HuR的差异表达在卵巢癌、胃癌和乳腺癌中具有预后意义。HuR通过细胞周期进程、侵袭和转移途径调节多种对肿瘤发生至关重要的蛋白质的表达。越来越多的证据表明血管生成途径也参与其中。使用定量自动免疫荧光显微镜系统（AQUA）对由560例结直肠腺癌患者的肿瘤组成的组织芯片进行HuR蛋白表达分析。通过机构审查委员会（IRB）批准的方案收集的与每个检测标本对应的临床数据，采用卡方检验、Cox回归和Kaplan-Meier分析进行分析。中位随访时间为54个月。与肿瘤分期和总体肿瘤-淋巴结-转移（TNM）分期一起，HuR表达被发现是生存的独立预测因素。在总HuR表达处于最高四分位数的患者中，生存期比处于较低四分位数的患者短22.8个月（40.6个月对63.4个月，p = 0.04）。此外，HuR水平与血管内皮生长因子（VEGF）和血管内皮标志物CD31的表达呈正相关。我们得出结论，高水平的HuR表达与晚期疾病特征相关，预示着结直肠腺癌患者的生存期较差。这些结果进一步表明，HuR通过VEGF介导的血管生成发挥其致瘤作用，可能是结直肠癌的一个新的治疗靶点。
