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唾液酸结合免疫球蛋白样凝集素8(Siglec-8)表达增强预示着透明细胞肾细胞癌患者的不良预后。

Enhancement of Siglec-8 expression predicts adverse prognosis in patients with clear cell renal cell carcinoma.

作者信息

Ou Chenzhang, Liu Li, Wang Jiajun, Dai Siyuan, Qu Yang, Xiong Ying, Xi Wei, Xu Jiejie, Guo Jianming

机构信息

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Urol Oncol. 2017 Oct;35(10):607.e1-607.e8. doi: 10.1016/j.urolonc.2017.05.016. Epub 2017 Jun 12.

DOI:10.1016/j.urolonc.2017.05.016
PMID:28619634
Abstract

PURPOSE

Sialic acid-binding immunoglobulin-like lectins (siglecs) family has important functions in tumor progression. The purpose of our study is to figure out the correlation between the expression level of Siglec-8 and prognosis of patients with clear cell renal cell carcinoma (ccRCC), and then to predict the overall survival (OS) via a novel nomogram.

MATERIALS AND METHODS

A group of patients (n = 267) histologically diagnosed with ccRCC from Zhongshan Hospital were included into our study. Immunohistochemistry of Siglec-8 was performed in the tissue microarray, and the staining intensity was divided into high/low according to the median value of the H-score grading. Survival analyses including Kaplan-Meier analyses and Cox regression analyses were performed to evaluate the association between Siglec-8 expression and the survival of patients in different risk groups. Stage, size, grade, and necrosis score and University of California Los Angeles Integrated Staging System score were used in the risk stratification. A nomogram incorporating Siglec-8 and several other clinical parameters was plotted for predicting the 5-year and 8-year OS.

RESULTS

Siglec-8 was observed dominantly on the membrane of tumor cells. The enhanced expression level of Siglec-8 had significant correlation with adverse overall and disease-free survival of patients (P<0.0001 and P = 0.0186, respectively). The association was more significant in patients with lower risk. Cox regression analyses defined Siglec-8 as an independent prognostic factor of OS (P<0.001 for univariate analysis, P = 0.003 for multivariate analysis). The new nomogram integrating Siglec-8 with several traditional prognostic factors proved to be more accurate than conventional prognostic system using tumor node metastasis stage only (Harrell c-index: 0.801, 95% CI: 0.755-0.847 vs. 0.717, 95% CI: 0.662-0.772).

CONCLUSION

Our study has found that the elevated expression level of Siglec-8 was correlated with poor prognosis of patients with ccRCC. Siglec-8, incorporation with other clinical parameters, could perform better in prediction of patients׳ OS.

摘要

目的

唾液酸结合免疫球蛋白样凝集素(Siglecs)家族在肿瘤进展中具有重要作用。本研究旨在明确Siglec-8表达水平与透明细胞肾细胞癌(ccRCC)患者预后之间的相关性,进而通过一种新型列线图预测总生存期(OS)。

材料与方法

纳入中山大学附属中山医院一组经组织学诊断为ccRCC的患者(n = 267)。在组织芯片上进行Siglec-8免疫组化检测,并根据H评分分级的中位数将染色强度分为高/低。进行生存分析,包括Kaplan-Meier分析和Cox回归分析,以评估Siglec-8表达与不同风险组患者生存之间的关联。风险分层采用分期、大小、分级、坏死评分和加利福尼亚大学洛杉矶分校综合分期系统评分。绘制包含Siglec-8和其他几个临床参数的列线图,用于预测5年和8年总生存期。

结果

Siglec-8主要在肿瘤细胞膜上表达。Siglec-8表达水平升高与患者不良的总生存期和无病生存期显著相关(分别为P<0.0001和P = 0.0186)。在低风险患者中这种关联更为显著。Cox回归分析将Siglec-8定义为总生存期的独立预后因素(单因素分析P<0.001,多因素分析P = 0.003)。将Siglec-8与几个传统预后因素相结合的新列线图被证明比仅使用肿瘤淋巴结转移分期的传统预后系统更准确(Harrell c指数:0.801,95%CI:0.755 - 0.847 vs. 0.717,95%CI:0.662 - 0.772)。

结论

我们的研究发现Siglec-8表达水平升高与ccRCC患者预后不良相关。Siglec-8与其他临床参数相结合,在预测患者总生存期方面表现更佳。

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