Abstract. Although it is the most widely used biomarker for prostate cancer, the use of prostate specific antigen (PSA) is controversial due to its limitations in specificity and sensitivity. The proteasome is a complex associated with cell proliferation and apoptosis, and the abnormity of these processes may lead to tumor occurrence. Previous studies have reported that proteasomal activity is associated with cancer progression and can be used in risk stratification. The purpose of the present study was thus to investigate the feasibility of proteasome activity as a biomarker for prostate cancer. Proteasome activity in vitro and in vivo was detected, along with the expression of the substrate proteins NF-κB inhibitor-α (IκB-α), Bcl-2-associated X (Bax) and p27. Chymotrypsin-like proteasomal activity was elevated by 70% in vitro and 23% in vivo, and the expression levels of the proteasome substrate proteins IκB-α, Bax and p27 were decreased in prostate cancer cells and prostate tumor xenografts compared with normal mouse prostate tissue. In conclusion, proteasomal chymotrypsin-like activity maybe a potential biomarker for prostate cancer, and may be suitable to supplement PSA in clinical application for prostate cancer diagnosis.
IntroductionProstate cancer is the most commonly diagnosed malignancy in men in western countries (1). As the second most common cause for cancer-associated mortality among men, prostate cancer caused ~27,540 deaths in the United States (2015) (2).In addition, the incidence and mortality for prostate cancer have been evidently increasing in Asia, including in China, in recent years (3).Although novel therapies for prostate cancer with proven survival benefits have been developed relatively recently (4,5), the overall increase in survival rate has been negligible. A major clinical challenge in prostate cancer is the insufficient power of the currently available diagnostic tests. Since the introduction of serum prostate specific antigen (PSA) screening >30 years ago, prostate cancer diagnosis and management have been guided by this biomarker; it remains the most commonly used tumor marker for prostate cancer diagnosis, postoperative monitoring and prognosis evaluation. PSA is a protein secreted by the epithelial cells of the prostate; an increase in serum PSA is often identified in prostate cancer patients (6,7). However, PSA is susceptible to various confounding factors, including benign prostatic hyperplasia, prostatitis and urethral surgery, which may influence the clinical reliability (8,9). The deficiencies of PSA, including the lack of specificity and sensitivity, may lead to false-positive or false-negative results. In view of this, identifying a biomarker with an improved diagnostic and prognostic potential for prostate cancer assessment may be of great significance.Refinements to PSA measurements have been proposed, including early PSA, benign PSA, free PSA, dynamic PSA parameters (including PSA velocity and PSA doubling time), PSA density (PSA to prostate volume ratio) and age-sp...