Abstract
Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer.
Highlights
An elevated prostate-specific antigen (PSA) level and abnormal digital rectal examination (DRE) finding will prompt the clinician to perform a prostate needle biopsy for the diagnosis of prostate cancer
We developed a lectin-antibody ELISA for the detection of Lewis-type or core-type fucosylated PSA (Fuc-PSA) and coretype Fuc-PSA
The urinary PSA-Aleuria aurantia lectin (AAL) and PSA-Pholiota squarrosa lectin (PhoSL) levels were significantly higher in patients with negative biopsy than in the patients with prostate cancer (P = 0.026 and P = 0.0001, respectively) (Figure 1)
Summary
An elevated prostate-specific antigen (PSA) level and abnormal digital rectal examination (DRE) finding will prompt the clinician to perform a prostate needle biopsy for the diagnosis of prostate cancer. Up to 40% of patients newly diagnosed with prostate cancer are categorized as low risk [1], in that they have a very limited possibility of disease progression and do not require definitive therapy. The search for a new marker associated with the high risk for prostate cancer is necessary. We have previously reported a high expression of serum fucosylated haptoglobin (which is associated with the GS) and α1-6 fucosyltransferase in prostate cancer cells [6]. PSAs have one N-glycosylation site, and 70% of the molecules contained a fucose group [7]. These findings led us to hypothesize that fucosylated PSAs (Fuc-PSAs) might be a predictor of prostate cancer, especially of the high-risk type
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