title: 8-hydroxydeguanosine and nitrotyrosine are prognostic factors in urinary bladder carcinoma.
abstract: Oxidative stress markers and peroxiredoxins are connected to cancer. A large set of urinary bladder carcinomas were studied for the expression of nitrotyrosine and 8-hydroxydeguanosine (8OHdG), two markers indicating oxidative damage. Serum and urine 8-OHdG were assessed in a subset of patients. We also analysed immunohisto-chemically the expression of nrf2, keap1, all six peroxiredoxins (prx) and thioredoxin (trx) in these tumors. 15 % of the cases showed 8OHdG and 36 % nitrotyrosine positivity. Expression of nitrotyrosine and 8OHdG associated with a poor prognosis (p=0.050, p=0.011, respectively). Peroxiredoxin positivity ranged from 39 % to 84 % lowest expression being for prx 4 and highest for prx 3. Prx 4 expression associated with a poor prognosis (p=0.025) with high grade (p=0.044) and larger tumors (p=0.023). Cytoplasmic trx positivity was seen in 91 % and nuclear in 59 % of tumors. Nuclear and cytoplasmic trx associated with each other (p<0.001), and nuclear trx associated with prx 6 (p=0.001), prx 2 (p<0.001), and prx 5 (p<0.001). 8OHdG associated with nuclear trx positivity (p=0.002), inversely with prx 1 (p=0.025) and with keap1 (p=0.020). Nuclear nrf2 was associated with nitrotyrosine (p=0.042). The results show that the amount of oxidative stress in urinary bladder tumors affects the prognosis of the patients. Of antioxidative enzymes, prx4 associated with an unfavourable prognosis. Selective inhibition of prx4 expression might then be one additional option of treatment of bladder cancer.
authors.affiliation: Department of Clinical Pathology and Forensic Medicine, Institute of Clinical Medicine, School of Medicine, Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland. ylermi.soini@uef.fi
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.forename: Kirsi-Maria
authors.initials: KM
authors.lastname: Haapasaari
authors.forename: Markku H
authors.initials: MH
authors.lastname: Vaarala
authors.forename: Taina
authors.initials: T
authors.lastname: Turpeenniemi-Hujanen
authors.forename: V
authors.initials: V
authors.lastname: Kärjä
authors.forename: Peeter
authors.initials: P
authors.lastname: Karihtala
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D054464:Peroxiredoxins / Q000378:metabolism; D011379:Prognosis; D018709:Statistics, Nonparametric; D013879:Thioredoxins / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C002744:3-nitrotyrosine; D014443:Tyrosine; D013879:Thioredoxins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D054464:Peroxiredoxins; D003849:Deoxyguanosine