Abstract 2872: Serum fucosylated haptoglobin is a novel prognostic biomarker for prostate cancer: Detailed analyses of its oligosaccharide structures

Fucosylation is a crucial oligosaccharide modification in cancer and inflammation, which is catalyzed by alpha 1-3 (Futs3-7and Futs9-11)/ alpha 1-6(Fut8) fucosyltransferases. Alpha1-3 fucosyltransferase is involved in synthesis of Lewis type fucosylation and alpha 1-6 fucosylation is involved in core fucosylation. We have reported that fucosylated haptoglobin (Fuc-Hpt) is a cancer biomarker for patients with pancreatic cancer and colorectal cancer, and developed a lectin-antibody ELISA to measure serum levels of Fuc-Hpt. In the present study, we evaluated serum Fuc-Hpt levels in patients with localized prostate cancer and analyzed the molecular mechanisms in terms of the sources of Fuc-Hpt producing tissue. Methods: Fuc-Hpt levels in 98 preoperative serum samples from patients who underwent radical prostatectomy (RP) were measured by lectin-antibody ELISA. Expression of Fut8 and haptoglobin proteins in prostate cancer cell lines (LnCAP, 22Rv1, DU145, and PC3) and prostatectomy specimens were analyzed by Western blot and immunohistochemical analysis, respectively. Site-specific N-glycan analyses of haptoglobin in sera obtained from patients with prostate cancer were performed using liquid chromatography-electrospray ionization mass spectrometry. Results: Fuc-Hpt levels were significantly associated with Gleason score (GS), but not with PSA levels. The area under the receiver-operator characteristics curve (AUC) for Fuc-Hpt of the prediction of Gleason score 7 or more in prostatectomy specimens was 0.753, in contrast to the PSA AUC of 0.561 and the PSAD AUC of 0.558. The Fuc-Hpt AUC of the prediction of GS upgrading from biopsy GS6 to RP GS7 or more was 0.689, in contrast to the PSA AUC of 0.588 and the PSAD AUC of 0.557. Multivariable analysis revealed that Fuc-Hpt levels were significantly associated with biochemical recurrence after prostatectomy. Western blot analysis showed that prostate cancer cells expressed both Fut8 and haptoglobin. Immunohistochemical analysis showed positive Fut8 and haptoglobin staining in prostate cancer cells in prostatectomy specimens. Mass spectrometry analyses demonstrated that the oligosaccharide structure of Fuc-Hpt from men with prostate cancer was different from that from patients with gastrointestinal cancer. Conclusions: Fuc-Hpt in sera of patients with prostate cancer is mainly core Fuc-Hpt, but not Lewis type Fuc-Hpt. It is suggested that Fuc-Hpt is produced from prostate cancer cells. Elevations in serum Fuc-Hpt fro