title: Nuclear 8-hydroxy-2'-deoxyguanosine as survival biomarker in patients with cutaneous melanoma.
abstract: 8-hydroxy-2'-deoxyguanosine (8-OHdG) is one of the main mutagenic modifications induced in DNA by oxidative stress. Elevated levels of 8-OHdG have been regarded as an independent prognostic factor in different types of cancer. Various enzymes, such as human 8-oxoguanine DNA-glycosylase 1 (hOGG1) and glucose-6-phosphate dehydrogenase (G6PD), act as protection against oxidative stress. The low activity of such enzymes has been consistently associated with increased risk of progression in several tumor types. The aim of this study was to investigate whether 8-OHdG, hOGG1 and G6PD expression in tumor tissues might be a predictor of survival in melanoma patients. The expression of 8-OHdG, hOGG1 and G6PD was immunohistochemically investigated in primary cutaneous melanoma and the effect on survival was analyzed. Furthermore, the immunostaining for p53 and survivin was evaluated and the relationship among 8-OHdG, hOGG1, G6PD, p53 and survivin expression was analyzed. Kaplan-Meier analysis demonstrated that patients with low expression of nuclear 8-OHdG had significantly longer survival time compared with those with a high expression (P=0.032), whereas cancer-specific survival of patients was not associated with hOGG1 or G6PD expression. These results suggest an involvement of oxidative DNA damage in the process of melanoma pathogenesis and demonstrate that 8-OHdG expression in nuclei of tumor cells could be useful as an early independent prognostic marker in patients with primary cutaneous melanoma.
authors.affiliation: Department of Cytomorphology, University of Cagliari, Italy Cittadella Universitaria, 09042 Monserrato (CA), Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Murtas
authors.forename: Franca
authors.initials: F
authors.lastname: Piras
authors.forename: Luigi
authors.initials: L
authors.lastname: Minerba
authors.forename: Jorge
authors.initials: J
authors.lastname: Ugalde
authors.forename: Carlo
authors.initials: C
authors.lastname: Floris
authors.forename: Cristina
authors.initials: C
authors.lastname: Maxia
authors.forename: Paolo
authors.initials: P
authors.lastname: Demurtas
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Perra
authors.forename: Paola
authors.initials: P
authors.lastname: Sirigu
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality*; D008875:Middle Aged; D011379:Prognosis; D012878:Skin Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine