Expression of Cytoplasmic 8-oxo-Gsn and MTH1 Correlates with Pathological Grading in Human Gastric Cancer

Background: Cancers have dysfunctional redox regulation resulting in production of reactive oxygen species(ROS), damaging DNA, RNA and free NTPs, and causing the accumulation of oxidative nucleic acids in cytoplasm.The major types are 8-oxo-7,8-dihydroguanine(8-oxoGsn) in RNA and 8-oxo-7,8-dihydro-2’ deoxyguanosine(8-oxodGsn) in Mt-DNA. The MTH1 protein sanitizes oxidized nucleotide pools from NTPs to monophosphates,preventing the occurrence of transversion mutations. This study concerned cytoplasmic 8-oxodGsn/Gsn andMTH1 expression in gastric cancer and para-cancer tissues and elucidated roles of nucleic-acid oxidation andanti-oxidation. Materials and
Methods: A polymer HRP detection system was used to detect 8-oxo-Gsn/dGsnand MTH1 expression in 51 gastric cancer and para-cancer tissue samples. Analyses of patient clinical andpathological data were also performed.
Results: The expression of MTH1 and the 8-oxo-dGsn/Gsn ratio weresignificantly higher in cancer tissues than para-cancer tissues (P<0.05). Cytoplasmic 8-oxo-Gsn and MTH1 wereboth found to positively correlate (P<0.05) with tumor differentiation, while no significant associations werefound with gender, age, invasion depth, lymph node metastasis and clinical stage (P>0.05).
Conclusions: We found8-oxo-dGsn/Gsn and MTH1 are both highly expressed in gastric cancer tissues, especially in well differentiatedlesions. In addition, oxidated mtDNA is prevalently expressed in gastric cancers, while 8-oxo-Gsn expression incytoplasmic RNA is a bit lower, but more selectively.