title: Receptors for advanced glycation end products (RAGE) is associated with microvessel density and is a prognostic biomarker for clear cell renal cell carcinoma.
abstract: The receptor for advanced glycation end products (RAGE) is involved in a variety of biological processes, including tumorigenisis. Previous studies have demonstrated that RAGE regulates the neo-angiogenesis related downstream molecule - vascular endothelial growth factor receptor 2 (VEGFR-2). Here, we investigated the potential relationship between RAGE, VEGFR-2 and angiogenesis in 80 renal cell carcinoma (RCC) patients. Real-time quantitative PCR and ELISA analysis were used to explore the RAGE and VEGFR-2 gene expression levels and the protein of VEGFR-2 expression. Meanwhile, angiogenesis was detected by the semi-quantification of endothelial cell marker CD34 combined with caldesmon, which was detected by microvessel density (MVD) technique and immunohistochemistry. Tumors were classified as low or high RAGE-expressing using the median as the cut-off. Immunofluorescence staining for RAGE protein was performed as well. Additionally, the median gene expression levels of VEGFR-2 in the tumors were significantly lower expressing low levels of RAGE expression, 0.34 (95% CI, 0.28-0.39) compared to the expressing high levels of RAGE expression, 0.45 (95% CI, 0.29-0.61), (P=0.03). The median MVD was significantly lower in the tumors expressing low levels of RAGE, 6.5 (95% CI, 6.21-7.43), compared to the expressing high levels, 7.9 (95% CI, 6.25-8.93), (P<0.01). Further, a positive association was certified with VEGFR-2 protein levels, P=0.07. Besides, RCC with high levels of RAGE expression are associated with high VEGFR-2 mRNA/protein levels and a higher density of microvessels; conversely, Kaplan-Meier survival analysis suggests that a significant correlation of elevated RAGE expression with decreased overall survival and metastasis-free survival. Our results establish that RAGE was identified as a potential prognostic biomarker for disease prognosis of RCC.
authors.affiliation: Transplantation Centre, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325014, China. Electronic address: yongguo_wzmu@126.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Transplantation Centre, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325014, China. Electronic address: xiapeng_wzmu@126.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Xia
authors.affiliation: Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325014, China. Electronic address: zhengjj@163.com.
authors.forename: Jian-Jian
authors.initials: JJ
authors.lastname: Zheng
authors.affiliation: Transplantation Centre, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325014, China. Electronic address: sunxb@163.com.
authors.forename: Xian-Bin
authors.initials: XB
authors.lastname: Sun
authors.affiliation: Transplantation Centre, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325014, China. Electronic address: pangxd@163.com.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Pan
authors.affiliation: Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325014, China. Electronic address: zhangxing@163.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Transplantation Centre, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325014, China. Electronic address: lxmlzr521@126.com.
authors.forename: Cun-Zao
authors.initials: CZ
authors.lastname: Wu
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D055806:Microvessels / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D000067759:Receptor for Advanced Glycation End Products / Q000096:biosynthesis*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D000067759:Receptor for Advanced Glycation End Products; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Metastasis; Prognosis; Receptor for advanced glycation end products (RAGE); Renal cell carcinoma; Vascular endothelial growth factor receptor 2