Nuclear oxidative damage correlates with poor survival in colorectal cancer.
Authors
Sheridan, JWang, L-M
Tosetto, M
Sheahan, K
Hyland, J
Fennelly, D
O'Donoghue, D
Mulcahy, H
O'Sullivan, J
Affiliation
Centre for Colorectal Disease, St Vincent's University Hospital, Elm Park Dublin , 4, Republic of Ireland.Issue Date
2012-02-01T10:28:49ZMeSH
AdolescentAdult
Aged
Aged, 80 and over
Apoptosis/physiology
Case-Control Studies
Cell Nucleus/*metabolism
Colon/metabolism/pathology
Colorectal Neoplasms/*metabolism/*mortality/pathology
Cytoplasm/metabolism
Deoxyguanosine/*analogs & derivatives/metabolism
Disease Progression
Female
Fluorescent Antibody Technique
Humans
Immunoenzyme Techniques
In Situ Nick-End Labeling
Male
Middle Aged
Rectum/metabolism/pathology
Superoxide Dismutase/metabolism
Survival Rate
Tissue Array Analysis
Tumor Markers, Biological/*metabolism
Young Adult
Metadata
Show full item recordCitation
Br J Cancer. 2009 Jan 27;100(2):381-8. Epub 2008 Dec 9.Journal
British journal of cancerDOI
10.1038/sj.bjc.6604821PubMed ID
19066606Abstract
Oxidative DNA damage results from DNA adducts such as 8-oxo-7, 8 dihydro-2'-deoxyguanosine (8-oxo-dG), which is a pro-mutagenic lesion. No known association between 8-oxo-dG, disease progression and survival exists in colorectal cancer (CRC). We examined levels of 8-oxo-dG in sporadic CRC to determine its relationship with pathological stage and outcome. A total of 143 CRC patients and 105 non-cancer patients were studied. Nuclear and cytoplasmic 8-oxo-dG was assessed using immunohistochemistry. Double immunofluorescence using 8-oxo-dG and manganese superoxide dismutase (MnSOD) antibodies localised cytoplasmic 8-oxo-dG. Apoptosis was detected using TUNEL. Nuclear staining levels were similar in tumour tissue and matched normal mucosa in both epithelial (P=0.22) and stromal (P=0.85) cells. Epithelial cytoplasmic staining was greater in tumour tissue (P<0.001). Double immunofluorescence localised cytoplasmic 8-oxo-dG to mitochondria. Epithelial and stromal nuclear 8-oxo-dG decreased with local disease spread, but highest levels were found in distant disease (P<0.01). Survival was related to epithelial nuclear and stromal staining in normal mucosa (P<0.001) and tumour (P<0.01) but was unrelated to cytoplasmic staining. Normal control cells in tissue from cancer patients with high levels of 8-oxo-dG failed to undergo cell death. 8-oxo-dG may be an important biomarker of disease risk, progression and survival for CRC patients.Language
engISSN
1532-1827 (Electronic)0007-0920 (Linking)
ae974a485f413a2113503eed53cd6c53
10.1038/sj.bjc.6604821
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