Fu Hangcheng, Liu Yidong, Xu Le, Chang Yuan, Zhou Lin, Zhang Weijuan, Yang Yuanfeng, Xu Jiejie
From the Department of Biochemistry and Molecular Biology (HF, YL, JX), Department of Immunology, School of Basic Medical Sciences (WZ), Department of Urology, Zhongshan Hospital, Fudan University (YC, LZ, YY), and Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China (LX).
Medicine (Baltimore). 2016 Apr;95(17):e3225. doi: 10.1097/MD.0000000000003225.
Mucin-4 (MUC4), a member of membrane-bound mucins, has been reported to exert a large variety of distinctive roles in tumorigenesis of different cancers. MUC4 is aberrantly expressed in clear-cell renal cell carcinoma (ccRCC) but its prognostic value is still unveiled. This study aims to assess the clinical significance of MUC4 expression in patients with ccRCC.The expression of MUC4 was assessed by immunohistochemistry in 198 patients with ccRCC who underwent nephrectomy retrospectively in 2003 and 2004. Sixty-seven patients died before the last follow-up in the cohort. Kaplan-Meier method with log-rank test was applied to compare survival curves. Univariate and multivariate Cox regression models were applied to evaluate the prognostic value of MUC4 expression in overall survival (OS). The predictive nomogram was constructed based on the independent prognostic factors. The calibration was built to evaluate the predictive accuracy of nomogram.In patients with ccRCC, MUC4 expression, which was determined to be an independent prognostic indicator for OS (hazard ratio [HR] 3.891; P < 0.001), was negatively associated with tumor size (P = 0.036), Fuhrman grade (P = 0.044), and OS (P < 0.001). The prognostic accuracy of TNM stage, UCLA Integrated Scoring System (UISS), and Mayo clinic stage, size, grade, and necrosis score (SSIGN) prognostic models was improved when MUC4 expression was added. The independent prognostic factors, pT stage, distant metastases, Fuhrman grade, sarcomatoid, and MUC4 expression were integrated to establish a predictive nomogram with high predictive accuracy.MUC4 expression is an independent prognostic factor for OS in patients with ccRCC.
黏蛋白4(MUC4)是膜结合黏蛋白的一员,据报道在不同癌症的肿瘤发生过程中发挥着多种独特作用。MUC4在透明细胞肾细胞癌(ccRCC)中异常表达,但其预后价值仍不明确。本研究旨在评估MUC4表达在ccRCC患者中的临床意义。通过免疫组织化学方法评估了2003年和2004年接受肾切除术的198例ccRCC患者中MUC4的表达情况。该队列中有67例患者在最后一次随访前死亡。采用Kaplan-Meier法和对数秩检验比较生存曲线。应用单因素和多因素Cox回归模型评估MUC4表达对总生存期(OS)的预后价值。基于独立预后因素构建预测列线图。建立校准以评估列线图的预测准确性。在ccRCC患者中,MUC4表达被确定为OS的独立预后指标(风险比[HR] 3.891;P<0.001),与肿瘤大小(P=0.036)、富尔曼分级(P=0.044)和OS(P<0.001)呈负相关。当加入MUC4表达时,TNM分期、加州大学洛杉矶分校综合评分系统(UISS)以及梅奥诊所分期、大小、分级和坏死评分(SSIGN)预后模型的预后准确性得到提高。将独立预后因素pT分期、远处转移、富尔曼分级、肉瘤样变和MUC4表达整合起来,建立了具有高预测准确性的预测列线图。MUC4表达是ccRCC患者OS的独立预后因素。