Preoperative Serum Caveolin-1 as a Prognostic Marker for Recurrence in a Radical Prostatectomy Cohort

Abstract

Purpose: Up-regulation of caveolin-1 (cav-1) is associated with virulent prostate cancer, and serum cav-1levels are elevated in prostate cancer patients but not in benign prostatic hyperplasia. In this study, we evaluated the potential of high preoperative serum cav-1 levels to predict biochemical progression of prostate cancer. The value of the combined preoperative markers, prostate-specific antigen (PSA), biopsy Gleason score, and serum cav-1for predicting biochemical recurrence was also investigated. Experimental Design: Serum samples taken from 419 prostate cancer patients before radical prostatectomy were selected from our Specialized Programs of Research Excellence prostate cancer serum and tissue bank. Serum samples were obtained 0 to 180 days before surgery and all patients had complete data on age, sex, race, stage at enrollment, and follow-up for biochemical recurrence. Serum cav-1 levels were measured according to our previously reported ELISA protocol.Results: Cav-1levels were measured in the sera of 419 prostate cancer patients; the mean serum level was 4.52 ng/mL (median 1.01ng/mL). Patients with high serum cav-1levels had a 2.7-fold (P = 0.0493) greater risk of developing biochemical recurrence compared with those with low serum cav-1levels. Importantly, patients with serum PSA z10 ng/mL and elevated levels of serum cav-1had 2.44 times higher risk (P = 0.0256) of developing biochemical recurrence compared with patients with low levels of cav-1. In addition, high serum cav-1levels combined with increasing biopsy Gleason score predicted much shorter recurrence-free survival in the group of patients with PSA z 10 ng/mL (P = 0.0353). Cav-1was also able to distinguish between high-and low-risk patients with biopsy Gleason score of seven, after adjusting, for patients PSA levels (P = 0.0429). Conclusions: Overall, elevated preoperative levels of serum cav-1 predict decreased time to cancer recurrence. In the subset of patients with serum PSA of z10 ng/mL, the combination of serum cav-1and biopsy Gleason score has the capacity to predict time to biochemical recurrence.

Caveolin-1 as a potential high-risk prostate cancer biomarker

“…When focused on prostate cancer, elevated caveolin-1 expression was observed in tumour tissue and in mice when compared to non-tumour tissue (64)(65)(66). According to Thompson et al, caveolin-1 is also elevated in the serum of patients with localized tumours compared to healthy controls and patients with benign prostatic hyperplasia (67,68). These findings are inconsistent with ours; we found no significant difference between controls and cancers.…”

Prognostic value of Caveolin‐1 in patients treated with radical prostatectomy: a multicentric validation study

“…Tahir et al [22] found higher levels of secreted Caveolin-1 in patients with prostate cancer compared with those with BPH or no evidence of prostate neoplasm. Furthermore, in a cohort of 414 patients with prostate cancer treated with RP, patients with higher preoperative Caveolin-1 levels had a 2.6-fold higher risk of BCR after RP than those with low levels [23]. In addition to its promising role as a biomarker, Caveolin-1 is being evaluated as a target for therapy.…”

Beyond prostate-specific antigen: alternate serum markers

“…Caveolin-1, a regulatory molecule involved in cell to cell signal transduction, has been shown to be overexpressed in advanced CaP and may have prognostic value as a serum marker. 122 E-cadherin, b-catenin and matrix metalloproteinases are also involved in altered cell adhesion and cellular migration and appear to be promising biological markers associated with disease aggressiveness. 123,124 Other potential protein biomarkers include inhibitors of metalloproteinases, 125 hepatocyte growth factor, 126 macrophage migration inhibitory factor, 127 progastrin-releasing peptide 128 and 50.8 kDa protein.…”