Abstract
ABSTRACTThe beta-2 adrenergic receptor (ADRB2) regulates the proliferation, apoptosis, angiogenesis, migration, and metastasis of cancer cells. However, its function in the progression of clear cell renal cell carcinoma (ccRCC) is unknown. Here, we report that ADRB2 can be a novel prognostic factor for patients with ccRCC. The differential expression of ADRB2 in low-stage (stages I and II), high-stage (stages III and IV), low-grade (grades I and II), and high-grade (grades III and IV) ccRCC was identified in cohorts of patients from The Cancer Genome Atlas and the International Cancer Genome Consortium. We evaluated ADRB2 expression as a prognostic factor using the Kaplan-Meier survival curve, multivariate analysis, time-dependent area under the curve (AUC) of Uno’s C-index, and AUC of the receiver operating characteristics (ROC) at five years. Kaplan-Meier analysis revealed that reduced ADRB2 expression is associated with poor prognosis in ccRCC patients. Analysis of C-indices and AUC-ROC further confirmed this result. Moreover, multivariate analysis confirmed the prognostic significance of ADRB2 expression. Collectively, these findings suggest that ADRB2 is a potential prognostic factor for ccRCC.
Highlights
Clear cell renal cell carcinoma is the most prevalent subtype of kidney cancer and approximately 30% of kidney cancer patients present with metastasis (Nickerson et al 2008)
Prognostic biomarkers for Clear cell renal cell carcinoma (ccRCC) have been investigated in cohorts of patients from The Cancer Genome Atlas (TCGA) (Cerami et al 2012; Cancer Genome Atlas Research et al 2013) and the International Cancer Genome Consortium (ICGC) (International Cancer Genome et al 2010)
We present the first data on ADRB2 expression in cohorts of patients with well-defined primary ccRCC from TGCA and ICGC and ADRB2 can be an important prognostic factor of ccRCC
Summary
Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of kidney cancer and approximately 30% of kidney cancer patients present with metastasis (Nickerson et al 2008). Beta-adrenergic receptors (βARs) are G proteincoupled receptors that regulate various cellular processes, including proliferation, invasion, and activation of the immune response (Barron et al 2012). The beta-2 adrenergic receptor (ADRB2) is the most abundant receptor for sympathetic signaling in prostate luminal cells (Braadland et al 2014). ADRB2 expression was decreased during prostate cancer metastasis (Yu et al 2007). We present the first data on ADRB2 expression in cohorts of patients with well-defined primary ccRCC from TGCA and ICGC and ADRB2 can be an important prognostic factor of ccRCC
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