Liu Yidong, Liu Haiou, Liu Weisi, Zhang Weijuan, An Huimin, Xu Jiejie
Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Mailbox 103, 138 Yixueyuan Road, Shanghai, 200032, China.
Department of Immunology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, 200032, China.
World J Urol. 2015 Nov;33(11):1791-9. doi: 10.1007/s00345-014-1451-x. Epub 2015 Jan 29.
β1,6-N-acetylglucosaminyltransferase V (MGAT5), which is required for the biosynthesis of β1,6GlcNAc-branched N-linked glycans attached to cell surface and secreted glycoproteins, accounts for oncogenic growth signal transduction during the development and progression of various malignancies. Our present study aimed to evaluate the impact of MGAT5 expression on recurrence and survival of patients with clear-cell renal cell carcinoma (ccRCC) following surgery.
We retrospectively enrolled 265 patients (196 in the training cohort and 69 in the validation cohort) with ccRCC undergoing nephrectomy at a single institution. Clinicopathologic features, overall survival (OS) and recurrence-free survival (RFS) were recorded. MGAT5 intensities were assessed by immunohistochemistry in specimens of patients. Kaplan-Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on OS and RFS. Concordance index (C-index) was calculated to assess predictive accuracy.
In both cohorts, MGAT5 expression positively correlated with metastatic and advanced TNM stage. High MGAT5 expression indicated poor survival (P < 0.001 in training set and P < 0.001 in validation set) and early recurrence (P < 0.001 in training set and P = 0.004 in validation set) of patients with ccRCC. After multivariate Cox regression analysis, MGAT5 expression was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of TNM, UISS and SSIGN prognostic models was improved when MGAT5 expression was added.
MGAT5 expression is a potential independent adverse prognostic biomarker for recurrence and survival of patients with ccRCC after nephrectomy.
β1,6-N-乙酰葡糖胺基转移酶V（MGAT5）是细胞表面和分泌型糖蛋白上β1,6-连接的N-乙酰葡糖胺（GlcNAc）分支型N-聚糖生物合成所必需的，在各种恶性肿瘤的发生发展过程中参与致癌生长信号转导。我们目前的研究旨在评估MGAT5表达对透明细胞肾细胞癌（ccRCC）患者术后复发和生存的影响。
我们回顾性纳入了在单一机构接受肾切除术的265例ccRCC患者（训练队列196例，验证队列69例）。记录临床病理特征、总生存期（OS）和无复发生存期（RFS）。通过免疫组织化学评估患者标本中的MGAT5强度。采用Kaplan-Meier法比较生存曲线。使用Cox回归模型分析预后因素对OS和RFS的影响。计算一致性指数（C-index）以评估预测准确性。
在两个队列中，MGAT5表达均与转移性和晚期TNM分期呈正相关。MGAT5高表达表明ccRCC患者生存较差（训练组P<0.001，验证组P<0.001）和早期复发（训练组P<0.001，验证组P=0.004）。多因素Cox回归分析后，MGAT5表达被确定为生存和复发的独立不良预后因素。加入MGAT5表达后，TNM、UISS和SSIGN预后模型的预测准确性得到提高。
MGAT5表达是ccRCC患者肾切除术后复发和生存的潜在独立不良预后生物标志物。
