Nuclear oxidative damage correlates with poor survival in colorectal cancer.
AffiliationCentre for Colorectal Disease, St Vincent's University Hospital, Elm Park Dublin , 4, Republic of Ireland.
Aged, 80 and over
Deoxyguanosine/*analogs & derivatives/metabolism
Fluorescent Antibody Technique
In Situ Nick-End Labeling
Tissue Array Analysis
Tumor Markers, Biological/*metabolism
MetadataShow full item record
CitationBr J Cancer. 2009 Jan 27;100(2):381-8. Epub 2008 Dec 9.
JournalBritish journal of cancer
AbstractOxidative 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.
- Immunohistochemical expression of 8-oxo-7,8-dihydro-2'-deoxyguanosine in cytoplasm of tumour and adjacent normal mucosa cells in patients with colorectal cancer.
- Authors: Matosevic P, Klepac-Pulanic T, Kinda E, Augustin G, Brcic I, Jakic-Razumovic J
- Issue date: 2015 Aug 7
- Localization of nuclear cathepsin L and its association with disease progression and poor outcome in colorectal cancer.
- Authors: Sullivan S, Tosetto M, Kevans D, Coss A, Wang L, O'Donoghue D, Hyland J, Sheahan K, Mulcahy H, O'Sullivan J
- Issue date: 2009 Jul 1
- Analysis of aromatic DNA adducts and 7,8-dihydro-8-oxo- 2'-deoxyguanosine in lymphocyte DNA from a case-control study of lung cancer involving minority populations.
- Authors: Vulimiri SV, Wu X, Baer-Dubowska W, de Andrade M, Detry M, Spitz MR, DiGiovanni J
- Issue date: 2000 Jan
- High clusterin expression correlates with a poor outcome in stage II colorectal cancers.
- Authors: Kevans D, Foley J, Tenniswood M, Sheahan K, Hyland J, O'Donoghue D, Mulcahy H, O'Sullivan J
- Issue date: 2009 Feb
- Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in normal colorectal mucosa: a randomized clinical trial.
- Authors: Fedirko V, Bostick RM, Long Q, Flanders WD, McCullough ML, Sidelnikov E, Daniel CR, Rutherford RE, Shaukat A
- Issue date: 2010 Jan