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Galectin-9 predicts postoperative recurrence and survival of patients with clear-cell renal cell carcinoma

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Tumor Biology

Abstract

Galectin-9 (Gal-9), a member of animal lectin family with evolutionary conserved carbohydrate recognition domains, has been reported to exert a large variety of functional roles in tumorigenesis due to its β-galactoside-binding affinity. The aim of this study is to evaluate the expression and prognostic significance of Gal-9 in patients with clear-cell renal cell carcinoma (ccRCC). The expression of Gal-9 was assessed by immunohistochemistry in 196 patients with ccRCC who underwent nephrectomy. In the cohort, 48 patients died and 61 patients suffered recurrence. Kaplan–Meier method with log–rank test was applied to compare survival curves. The authors employed univariate and multivariate Cox regression models to evaluate the prognostic value of Gal-9 expression in overall survival (OS) and recurrence-free survival (RFS). In patients with ccRCC, Gal-9 expression, which was positively associated with tumor size (P = 0.014), Fuhrman grade (P = 0.010), and necrosis (P = 0.025), was determined to be an independent prognostic indicator for OS (hazard ratio [HR] 2.394; P = 0.005) and RFS (HR 2.096; P = 0.006). High expression of Gal-9 was associated with poor survival (P = 0.001) and early recurrence (P = 0.006). Furthermore, Gal-9 expression could significantly stratify the patients in early (grades I + II) tumor, node, and metastasis (TNM) stage (OS: P = 0.005; RFS: P = 0.041) and low (grades 1 + 2) Fuhrman grade (OS: P = 0.004; RFS: P = 0.006). The prognostic accuracy of TNM, SSIGN, and UISS prognostic models was improved when Gal-9 expression was added. Gal-9 expression is a potential independent prognostic factor for OS and RFS in patients with ccRCC.

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Acknowledgments

We thank Ms. Haiying Zeng of the Department of Pathology, Zhongshan Hospital, Shanghai Medical College of Fudan University (Shanghai, China) for technical assistance. This study was funded by grants from the National Basic Research Program of China (2012CB822104), the National Natural Science Foundation of China (31100629, 31270863, 81471621, 81472227, and 81402085), the Program for New Century Excellent Talents in University (NCET-13-0146), and the Shanghai Rising-Star Program (13QA1400300). All these study sponsors have no roles in the study design and in the collection, analysis, and interpretation of data. This study was allowed by the Research Medical Ethics Committee of Fudan University. Informed consent was obtained from all individual participants included in the study.

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    Authors and Affiliations

    1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China

      Hangcheng Fu, Yidong Liu, Weisi Liu, Qiang Fu, Haiou Liu & Jiejie Xu

    2. Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

      Le Xu

    3. Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China

      Weijuan Zhang

    4. Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Mailbox 226, Shanghai, 200032, China

      Weijuan Zhang

    5. Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Mailbox 103, Shanghai, 200032, China

      Jiejie Xu

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    1. Hangcheng Fu
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    Correspondence to Weijuan Zhang or Jiejie Xu.

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    Hangcheng Fu and Yidong Liu contributed equally to this work.

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    Fig. S1

    The comparison of results between immunohistochemical analysis and immunoblot analysis. a Immunohistochemical analysis of tumor tissues from five patients with ccRCC; b Immunoblot analysis of tumor tissues from the corresponding five patients (GIF 306 kb)

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    Fu, H., Liu, Y., Xu, L. et al. Galectin-9 predicts postoperative recurrence and survival of patients with clear-cell renal cell carcinoma. Tumor Biol. 36, 5791–5799 (2015). https://doi.org/10.1007/s13277-015-3248-y

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