Department of Life Science, Pohang University of Science and Technology, Pohang, Korea.
Ann Surg Oncol. 2012 Jul;19 Suppl 3:S404-11. doi: 10.1245/s10434-011-1856-3. Epub 2011 Jun 30.
The aim of this study was to investigate the roles of renal tumor antigen (RAGE) in the progression and clinical outcome of hepatocellular carcinoma (HCC).
RAGE mRNA levels in 350 cases of HCC were investigated by quantitative real-time reverse transcription polymerase chain reaction. We analyzed the relationship of RAGE mRNA level with clinicopathologic parameters and clinical outcome. To identify the possible role of RAGE on cellular invasion, we performed in vitro analyses using small interfering RNAs (siRNAs).
RAGE mRNA level was significantly higher in HCC than in noncancerous hepatic tissues (P < 0.001). Overexpression of RAGE was significantly correlated with the presence of multiple tumors (P = 0.021), high alfa-fetoprotein level (P = 0.042), and advanced tumor stage (P = 0.016). Higher levels of RAGE expression were associated with significantly shorter overall survival time (P = 0.029). Knockdown of RAGE expression by siRNAs suppressed the invasive ability of HCC cells and the expression and secretion of matrix metalloproteinase-9 (MMP-9). We found that RAGE and MMP-9 expressions were correlated in HCCs, and furthermore, the combination of RAGE and MMP-9 expression was associated with the survival of patients (P = 0.0066).
Our results suggest that RAGE may be important in tumor invasion and could be a potential predictor for the prognosis of HCC patients.
本研究旨在探讨肾脏肿瘤抗原（RAGE）在肝细胞癌（HCC）进展和临床结局中的作用。
采用实时定量逆转录聚合酶链反应检测 350 例 HCC 中 RAGE mRNA 水平。分析 RAGE mRNA 水平与临床病理参数和临床结局的关系。为了确定 RAGE 对细胞侵袭的可能作用，我们使用小干扰 RNA（siRNA）进行了体外分析。
RAGE mRNA 水平在 HCC 中明显高于非癌性肝组织（P<0.001）。RAGE 过表达与多个肿瘤的存在显著相关（P=0.021）、高甲胎蛋白水平（P=0.042）和晚期肿瘤分期（P=0.016）。较高的 RAGE 表达水平与总生存时间显著缩短相关（P=0.029）。siRNA 下调 RAGE 表达抑制了 HCC 细胞的侵袭能力以及基质金属蛋白酶-9（MMP-9）的表达和分泌。我们发现 RAGE 和 MMP-9 在 HCC 中的表达相关，此外，RAGE 和 MMP-9 表达的组合与患者的生存相关（P=0.0066）。
我们的结果表明，RAGE 可能在肿瘤侵袭中起重要作用，并且可能是 HCC 患者预后的潜在预测因子。
