PSP94: Evaluation of Prognostic Utility in Patients Treated with Radiotherapy for Nonmetastatic Prostate Cancer

Abstract

Objectives: Conflicting reports exist as to the utility of PSP94 in the diagnosis and management of prostate cancer. We have identified serum‐bound forms of PSP94 in prostate cancer patients. To further evaluate the usefulness of this finding, we measured bound and free serum PSP94 levels in patients with nonmetastatic prostate cancer before radiotherapy. Materials and Methods: Pretreatment levels of free PSP94 in 42 patients were measured in serum via a competitive enzyme‐linked immunosorbent assay. Levels of bound PSP94 were measured by a semiquantitative assay after fractionation of total serum proteins by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and Western blot analysis. Pretreatment levels of prostate specific antigen (PSA) were measured by a commercially available assay. Archival sera from 42 patients and a subgroup of 27 patients with “favorable” pretreatment PSA values (i.e., < 10 ng/ml) were statistically analyzed. Pretreatment levels of PSP94 (free and bound) and PSA, as well as tumor stage and grade, were correlated with treatment outcome (biochemical relapse‐free survival) postradiotherapy. Results: Pretreatment PSA and the ratio of bound to free PSP94 were significant predictors of relapse postradiotherapy on univariate analysis. An elevated ratio of bound to free PSP94 was a stronger predictor (p = 0.0074) of relapse postradiotherapy compared with PSA level (p = 0.070) in a subgroup of prostate cancer patients with “favorable” pretreatment PSA levels. Conclusions: The results presented here indicate that serum PSP94‐bound complexes must be considered in evaluating the clinical utility of PSP94 as a prostate cancer marker. A higher ratio of bound to free PSP94 may indicate worse outcome postradiotherapy. Differential testing of serum PSP94 has shown that it, in addition to PSA, may be of prognostic value for patients receiving radiotherapy for nonmetastatic prostate cancer.

Prognostic Value of Prostate Secretory Protein of 94 Amino Acids and its Binding Protein after Radical Prostatectomy

“…This study follows on from previous work in which a multistep biochemical test was used to assess the relative levels of bound and free PSP94 in the initial serum of localized prostate cancer patients subsequently treated with radiation (13). In that study, the ratio of bound PSP94 to free PSP94 was an independent predictor of time to biochemical recurrence.…”

“…More recently, PSP94 was found to circulate in low and high molecular weight forms, suggesting the presence of a high -molecular weight blood-binding factor (9,12). In the pretreatment serum of patients treated with radiation, it was shown that tests differentiating between the free and bound forms of PSP94 had significant and independent prognostic value adjusting for initial PSA and Gleason score (13). More recently, a serum protein with high binding affinity for PSP94 (14), facilitating the development of monoclonal antibodies and immunoassays that specifically recognize the free and total forms of PSP94.…”

“…This retrospective study is a follow-up of a previous prognostic study (13) and uses new immunoassays to investigate whether pretreatment serum measurements of free PSP94, total PSP94, their ratios, or the PSP94-binding protein (PSPBP) have the potential to be useful prostate cancer prognostic factors using time to biochemical relapse as a surrogate end point following radical prostatectomy.…”

Prostate targeting: PSP94 gene promoter/enhancer region directed prostate tissue-specific expression in a transgenic mouse prostate cancer model

“…[31][32][33] Serumfree and bound forms of PSP94 were identified 31 and a new differential test between free and bound forms of PSP94 showed an improved prognostic value. 31,34 Studies in human, primate, pig, rat and mouse PSP94 have shown that PSP94, unlike rPB and PSA, is a conserved, but rapidly evolving protein, for a mini-review see Ref. 35.…”

Structural and molecular biology of PSP94 Its significance in prostate pathophysiology

“…Thus, investigators began to work towards identifying putative binding molecules of PSP94 that would enable development of serum immunoassays for PCa management by utilizing the bound and free forms of PSP94. Higher ratio of bound/free forms of serum PSP94 (sPSP94) compared to sPSA level in pretreatment samples was demonstrated to be a significant predictor of relapse post radiotherapy (110). Serum PSP94-bound complexes were later considered for evaluating the clinical utility of PSP94 as a marker for PCa progression.…”