Cui Zhi-Wen, Xia Ye, Ye Yi-Wang, Jiang Zhi-Mao, Wang Ya-Dong, Wu Jian-Ting, Sun Liang, Zhao Jun, Fa Ping-Ping, Sun Xiao-Juan, Gui Yao-Ting, Cai Zhi-Mingn
Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Centre, Shenzhen, China.
Asian Pac J Cancer Prev. 2012;13(7):3403-8. doi: 10.7314/apjcp.2012.13.7.3403.
The molecular mechanisms involved in the progression of clear cell renal cell carcinomas (ccRCCs) are still unclear. The aim of this study was to analyse the relationships between expression of RALYL and clinical characteristics. In 41 paired samples of ccRCCs and adjacent normal tissues, we used real-time qPCR to evaluate the expression of RALYL mRNA. RALYL protein levels were determined in 146 samples of ccRCC and 37 adjacent normal tissues by immunohistochemistry. Statistical analysis was used to explore the relationships between expression of RALYL and the clinical characteristics (gender, age, tumor size, T stage, N stage, M stage, survival times and survival outcome) in ccRCC. In addition, these patients were follow-up period 64 months (range: 4~116 months) to investigate the influence on prognosis. We found significantly differences between ccRCC tissues and normal tissues (p<0.001, paired-sample t test) in mRNA levels of RALYL. Immunohistochemistry analyses in 146 ccRCC samples and 37 adjacent normal tissues showed significantly lower RALYL protein levels in ccRCC samples (χ2-test, p<0.001), inversely correlating with tumour size (p=0.024), T stage (0.005), N stage (p<0.001) as well as M stage (p=0.019), but not age (p=0.357) and gender (p=0.348). Kaplan-Meier survival analysis demonstrated that people with lower level of RALYL expression had a poorer survival rate than those with a higher level of RALYL expression, significantly different by the log-rank test (p=0.011). Cox regression analysis indicated that RALYL expression (p=0.039), N stage (p=0.008) and distant metastasis (p<0.001) were independent prognosis factors for the overall survival of ccRCC patients. We demonstrated that the expression of RALYL was significantly low in ccRCC and correlated with a poor prognosis in a large number of clinical samples. Our findings showed that RALYL may be a potential therapeutic target as well as a poor prognostic factor.
透明细胞肾细胞癌（ccRCCs）进展过程中涉及的分子机制仍不清楚。本研究的目的是分析RALYL表达与临床特征之间的关系。在41对ccRCC及其相邻正常组织样本中，我们使用实时定量PCR评估RALYL mRNA的表达。通过免疫组织化学测定146例ccRCC样本和37例相邻正常组织中RALYL蛋白水平。采用统计学分析探讨ccRCC中RALYL表达与临床特征（性别、年龄、肿瘤大小、T分期、N分期、M分期、生存时间和生存结局）之间的关系。此外，对这些患者进行了64个月（范围：4~116个月）的随访，以研究其对预后的影响。我们发现ccRCC组织与正常组织之间RALYL的mRNA水平存在显著差异（配对样本t检验，p<0.001）。对146例ccRCC样本和37例相邻正常组织进行的免疫组织化学分析显示，ccRCC样本中RALYL蛋白水平显著降低（χ2检验，p<0.001），与肿瘤大小（p=0.024）、T分期（0.005）、N分期（p<0.001）以及M分期（p=0.019）呈负相关，但与年龄（p=0.357）和性别（p=0.348）无关。Kaplan-Meier生存分析表明，RALYL表达水平较低的患者生存率低于RALYL表达水平较高的患者，对数秩检验显示差异有统计学意义（p=0.011）。Cox回归分析表明，RALYL表达（p=0.039）、N分期（p=0.008）和远处转移（p<0.001）是ccRCC患者总生存的独立预后因素。我们证明，在大量临床样本中，ccRCC中RALYL的表达显著降低，且与预后不良相关。我们的研究结果表明，RALYL可能是一个潜在的治疗靶点以及不良预后因素。
