title: 8-Oxo-7,8-dihydroguanine and uric acid as efficient predictors of survival in colon cancer patients.
abstract: The aim of this work was to answer the question whether the broad range of parameters which describe oxidative stress and oxidatively damaged DNA and repair are appropriate prognosis factors of colon cancer (CRC) patients survival? The following parameters were analyzed for 89 CRC patients: concentration of uric acid and vitamins A, E, C in plasma; levels of 8-oxodGuo (8-oxo-7,8-dihydro-2'-deoxyguanosine) in DNA of leukocyte and colon tissues; urinary excretion rates of 8-oxodGuo and 8-oxoGua (8-oxo-7,8-dihydroguanine); the activity and mRNA or protein level of repair enzymes OGG1, APE1, ANPG, TDG and PARP1. All DNA modifications and plasma antioxidants were analyzed using high performance liquid chromatography (HPLC) or HPLC/gas chromatography-mass spectrometry techniques. Expression of repair proteins was analyzed by QPCR, Western or immunohistochemistry methods. Longer survival coincided with low levels of 8-oxodGuo/8oxoGua in urine and 8-oxodGuo in DNA as well as with high concentration of uric acid plasma level. In contrast to expectations, longer survival coincided with lower mRNA level in normal colon tissue of the main 8-oxoGua DNA glycosylase, OGG1, but no association was found for PARP-1 expression. When analyzing simultaneously two parameters the discriminating power increased significantly. Combination of low level of urinary 8-oxoGua together with low level of 8-oxodGuo in leukocyte (both below median value) or high concentration of plasma uric acid (above median value) have the best prediction power. Since prediction value of these parameters seems to be comparable to conventional staging procedure, they could possibly be used as markers to predict clinical success in CRC treatment.
authors.affiliation: Department of Clinical Biochemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Dziaman
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Banaszkiewicz
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Roszkowski
authors.forename: Daniel
authors.initials: D
authors.lastname: Gackowski
authors.forename: Ewa
authors.initials: E
authors.lastname: Wisniewska
authors.forename: Rafał
authors.initials: R
authors.lastname: Rozalski
authors.forename: Marek
authors.initials: M
authors.lastname: Foksinski
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Siomek
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Speina
authors.forename: Alicja
authors.initials: A
authors.lastname: Winczura
authors.forename: Andrzej
authors.initials: A
authors.lastname: Marszalek
authors.forename: Barbara
authors.initials: B
authors.lastname: Tudek
authors.forename: Ryszard
authors.initials: R
authors.lastname: Olinski
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality*; D004249:DNA Damage / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D008401:Gas Chromatography-Mass Spectrometry; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018384:Oxidative Stress; D011379:Prognosis; D015996:Survival Rate; D014527:Uric Acid / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D014527:Uric Acid; C024829:8-hydroxyguanine; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045643:DNA Repair Enzymes; D003849:Deoxyguanosine
keywords: 8-oxoGua; DNA damage/repair; colon cancer; oxidative stress; survival; uric acid