Fu Rong-Dang, Qiu Chun-Hui, Chen Hu-An, Zhang Zhi-Gang, Lu Min-Qiang
Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
Tumour Biol. 2014 Aug;35(8):7603-10. doi: 10.1007/s13277-014-2007-9. Epub 2014 May 6.
Retinoic acid receptor-related receptor alpha (RORalpha) has been proven to play a tumor suppressive role in certain types of solid tumors. However, the clinical characteristic of RORalpha has not been reported by far. This study investigated the expression of RORalpha in hepatocellular carcinoma (HCC) and evaluated its relationship with clinical parameters and prognosis in HCC patients. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot analyses were performed to detect RORalpha expression levels in 20 paired HCC and corresponding adjacent non-cancerous tissues. Immunohistochemistry was performed on 100 archived paraffin-embedded HCC samples. Statistical analyses evaluated the correlations between RORalpha expression and clinicopathological features. qRT-PCR showed that RORalpha mRNA expression was significantly down-regulated in tumors compared to the adjacent non-cancerous tissues, and Western blots found that RORalpha protein expression was also reduced in tumor tissues. Immunohistochemical assays revealed that decreased RORalpha expression was present in 65 % of HCC patients. Correlation analyses showed that RORalpha expression was significantly correlated with serum alpha fetoprotein (AFP, p = 0.005), pathology grade (p < 0.001), tumor recurrence (p = 0.008), and vascular invasion (p < 0.001). Kaplan-Meier analysis revealed that patients with low RORalpha expression levels had a shorter overall and disease-free survival than patients with high expression (p < 0.001 and p = 0.002, respectively). Multivariate regression analysis indicated that RORalpha was an independent predictor for overall survival and disease-free survival. In conclusion, the results of our study showed that down-regulated RORalpha expression was associated with poorer prognosis in HCC patients. RORalpha may be a new potential prognostic marker for HCC patients.
维甲酸受体相关受体α(RORα)已被证明在某些类型的实体瘤中发挥肿瘤抑制作用。然而,迄今为止,RORα的临床特征尚未见报道。本研究调查了RORα在肝细胞癌(HCC)中的表达,并评估其与HCC患者临床参数及预后的关系。采用定量逆转录聚合酶链反应(qRT-PCR)和蛋白质免疫印迹分析检测20对HCC及其相应癌旁非癌组织中RORα的表达水平。对100例存档的石蜡包埋HCC样本进行免疫组织化学检测。统计分析评估RORα表达与临床病理特征之间的相关性。qRT-PCR结果显示,与癌旁非癌组织相比,肿瘤组织中RORα mRNA表达显著下调,蛋白质免疫印迹分析发现肿瘤组织中RORα蛋白表达也降低。免疫组织化学检测显示,65%的HCC患者存在RORα表达降低。相关性分析表明,RORα表达与血清甲胎蛋白(AFP,p = 0.005)、病理分级(p < 0.001)、肿瘤复发(p = 0.008)及血管侵犯(p < 0.001)显著相关。Kaplan-Meier分析显示,RORα表达水平低的患者总生存期和无病生存期均短于高表达患者(分别为p < 0.001和p = 0.002)。多因素回归分析表明,RORα是总生存期和无病生存期的独立预测因子。总之,本研究结果表明,RORα表达下调与HCC患者预后较差相关。RORα可能是HCC患者一种新的潜在预后标志物。