title: A subclass of HER1 ligands are prognostic markers for survival in bladder cancer patients.
abstract: Members of the epidermal growth factor (EGF) family have been suggested as prognostic markers in patients with bladder cancer. Thus far, there has been no consensus on their usefulness. We report an analysis of six ligands and two receptors of which a subset correlate to tumor stage and survival. Biopsies from bladder cancer tumors were obtained from 73 patients followed for a median of 28 months. The mRNA content for six ligands [EGF, transforming growth factor alpha (TGF-alpha), amphiregulin (AR), betacellulin (betaCL), heparin-binding EGF-like growth factor (HB-EGF), epiregulin (EPI)] and two receptors [EGF receptor I Human EGF Receptor (HER1) and 2 (HER2)] was examined by a newly developed quantitative reverse transcription-PCR method. Five ligands and two receptors (HER1 and HER2) were present in median concentrations of (10(-21) mol/microg RNA) 0.39 (AR), 11 (betaCL), 2.4 (EPI), 40 (HB-EGF), 1.4 (TGF-alpha), 75 (HER1), and 39,000 (HER2). EGF was barely detectable. A significantly higher expression of EPI (P < 0.001), HB-EGF (P < 0.001), and TGF-alpha (P < 0.05) were observed in T2-T4 tumors as compared with Ta tumors. Especially the expression of EPI mRNA correlated strongly to survival (P < 0.0005), but increased expression of TGF-alpha (P < 0.005), AR, and HB-EGF (P < 0.02) was also associated with a reduced life span. For the first time, mRNA expression of six ligands and two receptors of the EGF family have been examined in bladder cancer tumors. Our data emphasize that members of the EGF family, especially EPI, may be potential bladder tumor markers.
authors.affiliation: Department of Clinical Biochemistry, Aarhus Kommune Hospital, DK 8000 Aarhus C, Denmark.
authors.forename: V B
authors.initials: VB
authors.lastname: Thøgersen
authors.forename: B S
authors.initials: BS
authors.lastname: Sørensen
authors.forename: S S
authors.initials: SS
authors.lastname: Poulsen
authors.forename: T F
authors.initials: TF
authors.lastname: Orntoft
authors.forename: H
authors.initials: H
authors.lastname: Wolf
authors.forename: E
authors.initials: E
authors.lastname: Nexo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066258:Amphiregulin; D066259:Betacellulin; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D066260:Epiregulin; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D066258:Amphiregulin; D066259:Betacellulin; D014408:Biomarkers, Tumor; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor; D066260:Epiregulin; D066246:ErbB Receptors; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha; C587848:AREG protein, human; C587851:BTC protein, human; C587880:EREG protein, human