Granulocyte macrophage colony-stimulating factor predicts postoperative recurrence of clear-cell renal cell carcinoma
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Yuan Chang1,*, Le Xu3,*, Lin Zhou1,*, Qiang Fu2, Zheng Liu2, Yuanfeng Yang1, Zongming Lin1, Jiejie Xu2
1Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
2Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
3Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
*These authors have contributed equally to this work
Zongming Lin, e-mail: email@example.com
Jiejie Xu, e-mail: firstname.lastname@example.org
Keywords: clear-cell renal cell carcinoma, granulocyte macrophage colony-stimulating factor, prognostic biomarker, recurrence-free survival, nomogram
Received: October 18, 2015 Accepted: February 29, 2016 Published: March 21, 2016
Background: Granulocyte macrophage colony-stimulating factor (GM-CSF) is currently widely used as an adjuvant in cancer immunotherapy. However, recent studies have shown that GM-CSF can impair anti-tumor immune responses. Thus the role of GM-CSF in clear-cell renal cell carcinoma (ccRCC) remains unraveled. Our present study aims to investigate the prognostic significance of intratumoral GM-CSF in patients with clinically localized ccRCC.
Results: A high intratumoral GM-CSF expression was significantly associated with lymph node metastases (P = 0.009), high TNM stage (P = 0.031), high Fuhrman grade (P < 0.001), presence of tumor necrosis (P = 0.005), and high Leibovich scores (P < 0.001). In addition, the prognostic significance of intratumoral GM-CSF expression was restricted to patients with Leibovich intermediate/high-risk (P = 0.001). Furthermore, a high intratumoral GM-CSF expression was demonstrated as an independent prognostic factor of reduced RFS (P = 0.018). Incorporation of the intratumoral GM-CSF expression into a prognostic model including TNM stage, Fuhrman grade, tumor necrosis and lymphovascular invasion generated a nomogram, which predicted accurately 3- and 5-year survival for ccRCC patients.
Materials and Methods: This study comprised 233 clinically localized (T1-3N0-1M0) ccRCC patients undergoing nephrectomy in 2008 at a single centre. Intratumoral GM-CSF expression was assessed by immunohistochemical staining and its associations with clinicopathologic features and recurrence-free survival (RFS) were evaluated.
Conclusions: The intratumoral GM-CSF expression, as a potentially independent prognostic biomarker for recurrence, might improve conventional clinical and pathologic analysis to refine outcome prediction for clinically localized ccRCC patients after surgery.
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