Serum fucosylated haptoglobin as a novel prognostic biomarker predicting high-Gleason prostate cancer

BACKGROUND: Fucosylation is an oligosaccharide modification associated with cancer and inflammation, which is catalyzed by fucosyltransferases. Fucosylated haptoglobin (Fuc-Hpt) has been identified as a novel biomarker for pancreatic cancer. In this study, we evaluated serum Fuc-Hpt as a biomarker for prostate cancer, and investigated the expression of fucosyltransferases and haptoglobin in prostate cancer cell lines. METHODS: We measured the preoperative serum Fuc-Hpt levels in 98 patients who underwent radical prostatectomy (RP) using an established lectin-antibody ELISA. Fucosyltransferase and haptoglobin mRNA and protein expressions in prostate cancer cell lines were determined using quantitative PCR and Western blotting. RESULTS: Serum Fuc-Hpt levels were significantly associated with Gleason score (GS), but not prostate-specific antigen (PSA) levels. The area under the receiver-operator characteristics curve (AUC) for the prediction of GS ≥7 in prostatectomy specimens by Fuc-Hpt was 0.753, in contrast to the PSA AUC of 0.561 and the PSAD AUC of 0.558. The Fuc-Hpt AUC for the prediction of GS upgrade from GS 6 at biopsy to GS ≥7 after RP was 0.689, in contrast to the PSA AUC of 0.588 and PSAD AUC of 0.557. Multivariable analysis revealed that Fuc-Hpt levels were significantly associated with biochemical recurrence after prostatectomy. A high expression of alpha-(1-6) fucosyltransferase (FUT8) and haptoglobin was observed in prostate cancer cell line, suggesting that certain kinds of prostate cancer cells produce Fuc-Hpt. CONCLUSION: Elevated serum Fuc-Hpt level could be a novel cancer biomarker for predicting the prognosis of patients with prostate cancer, particularly those with high GSs.