title: 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.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, USA.
authors.forename: Dali
authors.initials: D
authors.lastname: Huang
authors.forename: George P
authors.initials: GP
authors.lastname: Casale
authors.forename: Jun
authors.initials: J
authors.lastname: Tian
authors.forename: Subodh M
authors.initials: SM
authors.lastname: Lele
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Pisarev
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Simpson
authors.forename: George P
authors.initials: GP
authors.lastname: Hemstreet
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D015153:Blotting, Western; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011467:Prostate / Q000201:enzymology* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D040081:Protein Array Analysis / Q000379:methods; D012680:Sensitivity and Specificity; D014533:Uridine Diphosphate Glucose Dehydrogenase / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D014533:Uridine Diphosphate Glucose Dehydrogenase
references.citation: J Natl Cancer Inst. 2001 Mar 21;93(6):427-36
references.pmid: 11259468
references.citation: Cancer Biol Ther. 2007 May;6(5):763-8
references.pmid: 17592251
references.citation: Biochim Biophys Acta. 2002 Aug 19;1591(1-3):37-44
references.pmid: 12183053
references.citation: Histol Histopathol. 2008 Apr;23(4):391-5
references.pmid: 18228195
references.citation: Cancer Res. 2003 May 15;63(10):2638-44
references.pmid: 12750291
references.citation: Carcinogenesis. 2008 Feb;29(2):282-90
references.pmid: 18174258
references.citation: Am J Pathol. 2002 Sep;161(3):849-57
references.pmid: 12213713
references.citation: Oncogene. 2001 Apr 12;20(16):1981-9
references.pmid: 11360182
references.citation: J Natl Cancer Inst. 2006 Feb 15;98(4):255-61
references.pmid: 16478744
references.citation: Endocr Res. 2004 Nov;30(4):717-25
references.pmid: 15666817
references.citation: J Biochem Mol Toxicol. 2005;19(5):279-88
references.pmid: 16292757
references.citation: Oncologist. 2008 Mar;13(3):299-305
references.pmid: 18378540
references.citation: Cancer. 1953 Sep;6(5):963-8
references.pmid: 13094644
references.citation: Cancer Cell Int. 2007 Mar 15;7:2
references.pmid: 17362521
references.citation: Biochem Biophys Res Commun. 1997 Oct 29;239(3):775-81
references.pmid: 9367845
references.citation: BJU Int. 2004 Apr;93(6):822-6
references.pmid: 15049997
references.citation: J Biol Chem. 2007 Apr 6;282(14):10814-25
references.pmid: 17293599
references.citation: J Urol. 1998 Oct;160(4):1562-6
references.pmid: 9751413
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1371-81
references.pmid: 17623804
references.citation: J Transl Med. 2006 Mar 02;4:13
references.pmid: 16512911
references.citation: Lab Invest. 2000 Feb;80(2):199-208
references.pmid: 10701689
references.citation: Front Biosci. 2008 May 01;13:5664-80
references.pmid: 18508614
references.citation: Semin Cancer Biol. 2008 Aug;18(4):288-95
references.pmid: 18468453
references.citation: Endocrinology. 2006 Nov;147(11):5431-42
references.pmid: 16887906
references.citation: J Biol Chem. 2008 Jun 20;283(25):17635-51
references.pmid: 18441325
references.citation: BJU Int. 2005 Dec;96(9):1219-23
references.pmid: 16287434
references.citation: Int J Cancer. 1982 Jun 15;29(6):611-6
references.pmid: 7107064
references.citation: Gastroenterology. 2008 Feb;134(2):500-10
references.pmid: 18242216
references.citation: J Biol Chem. 2007 Jul 13;282(28):20561-72
references.pmid: 17502371
references.citation: Neoplasia. 2004 Nov-Dec;6(6):821-30
references.pmid: 15720809
references.citation: J Biochem. 2005 Jun;137(6):703-9
references.pmid: 16002992
references.citation: J Pathol. 1995 Nov;177(3):323-8
references.pmid: 8551396
references.citation: Prostaglandins Other Lipid Mediat. 2007 Jan;82(1-4):185-97
references.pmid: 17164146
references.citation: Cancer Res. 2005 Dec 1;65(23):10946-51
references.pmid: 16322242
references.citation: J Biol Chem. 2007 Nov 16;282(46):33466-33474
references.pmid: 17848572
references.citation: J Steroid Biochem Mol Biol. 2008 Apr;109(3-5):247-53
references.pmid: 18467088
references.citation: J Biochem Mol Biol. 2007 Mar 31;40(2):142-50
references.pmid: 17394762
references.citation: Neoplasia. 2004 Jan-Feb;6(1):41-52
references.pmid: 15068670
references.citation: Genes Dev. 2007 Aug 15;21(16):2005-17
references.pmid: 17699749
references.citation: CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
references.pmid: 18287387
references.citation: Cancer Res. 2004 Aug 15;64(16):5702-11
references.pmid: 15313910
references.citation: Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8287-91
references.pmid: 8367495
references.citation: Cancer Res. 2009 Mar 15;69(6):2332-9
references.pmid: 19244115
references.citation: J Biol Chem. 2002 Oct 25;277(43):40549-56
references.pmid: 12189136
references.citation: J Natl Cancer Inst. 2005 Dec 21;97(24):1808-15
references.pmid: 16368942
references.citation: Mol Pharmacol. 2009 Jul;76(1):47-57
references.pmid: 19372209
references.citation: Prostate. 2007 Sep 1;67(12):1265-76
references.pmid: 17597114
references.citation: Cytometry A. 2006 Jul;69(7):601-11
references.pmid: 16680710
references.citation: J Urol. 2007 Aug;178(2):375
references.pmid: 17561165
references.citation: Front Biosci. 2004 Sep 01;9:2671-9
references.pmid: 15358590
references.citation: J Biol Chem. 2003 Jun 13;278(24):21566-75
references.pmid: 12682078
references.citation: Br J Cancer. 2008 Feb 26;98(4):756-65
references.pmid: 18268494
references.citation: J Natl Cancer Inst. 2007 Sep 19;99(18):1395-400
references.pmid: 17848671
references.citation: J Biol Chem. 2001 Apr 13;276(15):11922-32
references.pmid: 11278412
references.citation: Carcinogenesis. 2007 Feb;28(2):310-20
references.pmid: 16864594
references.citation: Mol Cancer Ther. 2006 Oct;5(10):2512-21
references.pmid: 17041095
references.citation: Nat Med. 2002 Nov;8(11):1323-7
references.pmid: 12389040
references.citation: Biosci Biotechnol Biochem. 2006 Feb;70(2):401-10
references.pmid: 16495656
references.citation: Cancer Res. 2007 May 15;67(10):4807-15
references.pmid: 17510410
references.citation: Semin Cancer Biol. 2008 Aug;18(4):268-74
references.pmid: 18450474
references.citation: J Urol. 2004 Jun;171(6 Pt 1):2484-8
references.pmid: 15126881
references.citation: Int J Cancer. 2004 Oct 20;112(1):121-9
references.pmid: 15305383