Udp-glucose dehydrogenase as a novel field-specific candidate biomarker of prostate cancer.

Abstract

Uridine diphosphate (UDP)-glucose dehydrogenase (UGDH) catalyzes the oxidation of UDP-glucose to yield UDP-glucuronic acid, a precursor for synthesis of glycosaminoglycans and proteoglycans that promote aggressive prostate cancer (PC) progression. The purpose of our study was to determine if the UGDH expression in normal appearing acini (NAA) from cancerous glands is a candidate biomarker for PC field disease/effect assayed by quantitative fluorescence imaging analysis (QFIA). A polyclonal antibody to UGDH was titrated to saturation binding and fluorescent microscopic images acquired from fixed, paraffin-embedded tissue slices were quantitatively analyzed. Specificity of the assay was confirmed by Western blot analysis and competitive inhibition of tissue labeling with the recombinant UGDH. Reproducibility of the UGDH measurements was high within and across analytical runs. Quantification of UGDH by QFIA and Reverse-Phase Protein Array analysis were strongly correlated (r = 0.97), validating the QFIA measurements. Analysis of cancerous acini (CA) and NAA from PC patients vs. normal acini (NA) from noncancerous controls (32 matched pairs) revealed significant (p < 0.01) differences, with CA (increased) vs. NA, NAA (decreased) vs. NA and CA (increased) vs. NAA. Areas under the Receiver Operating Characteristic curves were 0.68 (95% CI: 0.59-0.83) for NAA and 0.71 (95% CI: 0.59-0.83) for CA (both vs. NA). These results support the UGDH content in prostatic acini as a novel candidate biomarker that may complement the development of a multi-biomarker panel for detecting PC within the tumor adjacent field on a histologically normal biopsy specimen.

• Authors: Dali Huang, George P Casale, Jun Tian, Subodh M Lele, Vladimir M Pisarev, Melanie A Simpson, George P Hemstreet 3rd
• Journal: International journal of cancer (Int J Cancer) Vol. 126 Issue 2 Pg. 315-27 (Jan 15 2010) ISSN: 1097-0215 [Electronic] United States
• PMID: 19676054 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Biomarkers, Tumor
• Uridine Diphosphate Glucose Dehydrogenase

Topics

• Aged
• Biomarkers, Tumor (metabolism)
• Biopsy
• Blotting, Western
• Cell Line, Tumor
• Humans
• Male
• Microscopy, Fluorescence
• Middle Aged
• Prostate (enzymology, pathology)
• Prostatic Neoplasms (diagnosis, enzymology, pathology)
• Protein Array Analysis (methods)
• Sensitivity and Specificity
• Uridine Diphosphate Glucose Dehydrogenase (metabolism)