Cao Dalong, Qu Yuanyuan, Zhang Xuan, Xu Fujiang, Zhou Shuxian, Zhang Guiming, Dai Bo, Zhu Yao, Shi Guohai, Shen Yijun, Zhu Yiping, Zhang Hailiang, Ye Dingwei, Zhao Jianyuan
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
J Cancer. 2018 Sep 8;9(18):3400-3406. doi: 10.7150/jca.23923. eCollection 2018.
Specific lifestyle factors including tobacco-exposure are vital etiologic factors for renal cell carcinoma (RCC), F2R Like Thrombin/Trypsin Receptor 3 (F2RL3) is associated with smoking but it is unknown whether its expression translate into poor survival of clear cell RCC (ccRCC). In the current study, the expression profiling and prognostic value of F2RL3 in Chinese patients with ccRCC were investigated. Using Quantitative PCR analysis and immunohistochemistry, the relative expression levels of F2RL3 in 367 paired ccRCC and adjacent normal tissues were calculated. Cox regression analysis was used to identify independent prognostic factors and Kaplan-Meier analysis and a log-rank test were employed to evaluate the prognostic value of F2RL3. We observed that high expression of F2RL3 mRNA and protein were strongly correlated with shorten progression-free survival (PFS) of ccRCC with hazard ratios (HR; 95% confidence interval (CI)) of 2.060 (1.410-3.009) and 1.657 (1.193-2.300), respectively, as well as with poor overall survival (OS) with HRs (95%CI) of 2.826 (1.713-4.662) and 1.712 (1.140-2.569), respectively. After adjustment for confounding factors including smoking status, elevated HRs (95%CI) of 2.113 (1.445-3.089) and 1.692 (1.218-2.352) were presented for PFS, respectively, and 2.936 (1.777-4.851) and 1.811 (1.203-2.725) were present for OS, respectively. Meanwhile, increased F2RL3 mRNA and protein level were reported to significantly associate with smoking-exposure and well-known prognostic factors (higher TNM stage and ISUP grade). These findings suggested that F2RL3 mRNA and protein level in ccRCC is a robust predictor of poorly prognostic phenotype. Exploring the causal relevance of F2RL3 in ccRCC development further warrants in the future study.
包括烟草暴露在内的特定生活方式因素是肾细胞癌(RCC)的重要病因,F2R样凝血酶/胰蛋白酶受体3(F2RL3)与吸烟有关,但尚不清楚其表达是否会导致透明细胞肾细胞癌(ccRCC)患者预后不良。在本研究中,我们调查了F2RL3在中国ccRCC患者中的表达谱及其预后价值。采用定量PCR分析和免疫组织化学方法,计算了367对ccRCC组织和癌旁正常组织中F2RL3的相对表达水平。采用Cox回归分析确定独立预后因素,并采用Kaplan-Meier分析和对数秩检验评估F2RL3的预后价值。我们观察到,F2RL3 mRNA和蛋白的高表达与ccRCC患者无进展生存期(PFS)缩短密切相关,风险比(HR;95%置信区间(CI))分别为2.060(1.410-3.009)和1.657(1.193-2.300),与总生存期(OS)缩短也密切相关,HRs(95%CI)分别为2.826(1.713-4.662)和1.712(1.140-2.569)。在调整包括吸烟状态在内的混杂因素后,PFS的HRs(95%CI)分别为2.113(1.445-3.089)和1.692(1.218-2.352),OS的HRs(95%CI)分别为2.936(1.777-4.851)和1.811(1.203-2.725)。同时,F2RL3 mRNA和蛋白水平的升高与吸烟暴露以及已知的预后因素(更高的TNM分期和ISUP分级)显著相关。这些结果表明,ccRCC中F2RL3 mRNA和蛋白水平是预后不良表型的有力预测指标。未来的研究有必要进一步探索F2RL3在ccRCC发生发展中的因果关系。