Abstract
The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa.
Highlights
Prostate cancer (PCa) is the most commonly diagnosed cancer and second leading cause of cancer death in men[1]
We detected a significant increase of FA2 and FM5A2G2S1 glycans in prostate cancer (PCa) compared with benign prostate hyperplasia (BPH)
Micro-grams of prostate specific antigen (PSA) are required for purification and characterization of the PSA glycan profile by the ultra performance liquid chromatography-mass spectrometric (UPLC-MS) method, a commonly used method in antibody drug quality control (QC) analysis
Summary
Prostate cancer (PCa) is the most commonly diagnosed cancer and second leading cause of cancer death in men[1]. PSA is confined to intact prostate tissue, and serum PSA level is very low. In disease conditions like PCa, the prostate structure is disrupted and PSA leaks into the circulation, resulting in an elevated serum PSA level. Serum PSA level has been widely used as a biomarker for PCa detection and progression monitoring. Serum PSA elevation is not cancer specific; PSA level increases in conditions such as benign prostate hyperplasia (BPH) or inflammation. Because of the low sensitivity of the PSA test, the wide use of serum PSA test has resulted in overdiagnosis and overtreatment of indolent PCa [3, 4]. Biomarkers that could effectively differentiate prostate cancer from benign prostate conditions and provide better guidance in clinical practice are needed
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