title: Potential survival markers in cancer patients undergoing chemotherapy.
abstract: Due to the importance of the identification of chemotherapy outcome prognostic factors, we attempted to establish the potential of oxidative stress/DNA damage parameters such as prognostic markers. The aim of the study was to determine whether platinum derivative-based chemotherapy in cancer patients (n = 66) is responsible for systemic oxidatively damaged DNA and whether damage biomarkers, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and the modified base 8-oxo-7,8-dihydroguanine (8-oxo-Gua), in urine and DNA may be used as a prognostic factor for the outcome of chemotherapy. All the aforementioned modifications were analyzed using techniques involving high-performance liquid chromatography/electrochemical detection (HPLC/EC) or HPLC/gas chromatography-mass spectrometry (GC-MS). Among all the analyzed parameters, the significantly decreased levels of 8-oxo-Gua in urine collected from a subgroup of patients 24 h after the first infusion of the drug, as compared with the baseline levels, correlated with a significantly longer overall survival (OS) (60 months after therapy) than in the subgroup without any decrease of this parameter after therapy (median OS = 24 months, p = 0.007). Moreover, a significantly longer OS was also observed in a group with increased urine levels of 8-oxo-dG after chemotherapy (38.6 vs. 20.5 months, p = 0.03). The results of our study suggest that patients with decreased 8-oxo-Gua levels and increased 8-oxo-dG levels in urine 24 h after the first dose should be considered as better responders to the administered chemotherapy, with a lower risk of death. The conclusion may permit the use of these parameters as markers for predicting the clinical outcome of platinum derivative-based chemotherapy.
authors.affiliation: Department of Clinical Biochemistry, Collegium Medicum, Nicolaus Copernicus University, Torun, Poland, roszkowskik@co.bydgoszcz.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Roszkowski
authors.forename: Jan
authors.initials: J
authors.lastname: Filipiak
authors.forename: Magdalena
authors.initials: M
authors.lastname: Wisniewska
authors.forename: Anna
authors.initials: A
authors.lastname: Mucha-Malecka
authors.forename: Pawel
authors.initials: P
authors.lastname: Basta
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents; D015415:Biomarkers / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000652:urine; D016903:Drug Monitoring; D004358:Drug Therapy; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018384:Oxidative Stress; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine