Co-expression of RAGE and HMGB1 is associated with cancer progression and poor patient outcome of prostate cancer

Am J Cancer Res. 2014 Jul 16;4(4):369-77. eCollection 2014.

Abstract

Receptor for advanced glycation end products (RAGE), along with its ligand high mobility group box 1 (HMGB1), is believed to play an important role in prostate cancer. The aim of this retrospective study was to investigate the expression of RAGE and HMGB1 and their clinical impact on prostate cancer progression and prognosis. The expression of RAGE and HMGB1 was assessed by immunohistochemistry in cancer lesions from 85 confirmed prostate cancer cases. We determined the potential association between the expression level of these two proteins and the clinicopathological features and overall patient survival. RAGE and HMGB1 were expressed in 78.8% (67/85) and 68.2% (58/85) cases of prostate cancer, respectively, and in the majority (54/85) of cases, these two proteins were co-expressed. There was a strong correlation between RAGE and HMGB1 expressions (P<0.001). The expression of RAGE, HMGB1 and their co-expression were all associated with advanced tumor clinical stage (P<0.05 for all). RAGE expression was also associated with the prostate specific antigen (PSA) level (P=0.014). However, neither the individual expression of those genes nor their co-expression was significantly related with age or Gleason score. The co-expression of RAGE and HMGB1 was associated with poor overall survival in patients with stage III and IV prostate cancer (P=0.047). These results suggest that the expression of RAGE and HMGB1 is associated with the progression and poor prognosis of prostate cancer. RAGE and HMGB1 could be new prognostic biomarkers for prostate cancer as well as molecular target for novel forms of therapies.

Keywords: HMGB1; RAGE; prognosis; progression; prostate cancer.