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

Prostate. 2014 Jul;74(10):1052-8. doi: 10.1002/pros.22824. Epub 2014 May 7.

Abstract

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.

Keywords: fucosylation; fucosyltransferase; haptoglobin; prostate cancer; tumor marker.

MeSH terms

  • Aged
  • Area Under Curve
  • Biomarkers, Tumor / blood*
  • Cell Line, Tumor
  • Fucosyltransferases / genetics
  • Haptoglobins / analysis*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prognosis
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Haptoglobins
  • Fucosyltransferases
  • Glycoprotein 6-alpha-L-fucosyltransferase
  • Prostate-Specific Antigen