J Pathol Transl Med.  2019 Jul;53(4):217-224. 10.4132/jptm.2019.02.20.

Association between Expression of 8-OHdG and Cigarette Smoking in Non-small Cell Lung Cancer

Affiliations
  • 1Department of Pathology, Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, Jeonju, Korea. mjchung@jbnu.ac.kr
  • 2Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, Jeonju, Korea.
  • 3Department of Thoracic and Cardiovascular Surgery, Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, Jeonju, Korea.
  • 4Department of Pharmacology, Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, Jeonju, Korea.

Abstract

BACKGROUND
Exposure to cigarette smoking (CS) is a major risk factor for the development of lung cancer. CS is known to cause oxidative DNA damage and mutation of tumor-related genes, and these factors are involved in carcinogenesis. 8-Hydroxydeoxyguanosine (8-OHdG) is considered to be a reliable biomarker for oxidative DNA damage. Increased levels of 8-OHdG are associated with a number of pathological conditions, including cancer. There are no reports on the expression of 8-OHdG by immunohistochemistry in non-small cell lung cancer (NSCLC).
METHODS
We investigated the expression of 8-OHdG and p53 in 203 NSCLC tissues using immunohistochemistry and correlated it with clinicopathological features including smoking.
RESULTS
The expression of 8-OHdG was observed in 83.3% of NSCLC. It was significantly correlated with a low T category, negative lymph node status, never-smoker, and longer overall survival (p < .05) by univariate analysis. But multivariate analysis revealed that 8-OHdG was not an independent prognostic factor for overall survival in NSCLC patients. The aberrant expression of p53 significantly correlated with smoking, male, squamous cell carcinoma, and Ki-67 positivity (p < .05).
CONCLUSIONS
The expression of 8-OHdG was associated with good prognostic factors. It was positively correlated with never-smokers in NSCLC, suggesting that oxidative damage of DNA cannot be explained by smoking alone and may depend on complex control mechanisms.

Keyword

Carcinoma, non-small cell lung; 8-Oxo-7-hydrodeoxyguanosine; p53; Smoking; Immunohistochemistry

MeSH Terms

Carcinogenesis
Carcinoma, Non-Small-Cell Lung*
Carcinoma, Squamous Cell
DNA
DNA Damage
Humans
Immunohistochemistry
Lung Neoplasms
Lymph Nodes
Male
Multivariate Analysis
Risk Factors
Smoke
Smoking*
Tobacco Products*
DNA
Smoke

Figure

  • Fig. 1. Immunohistochemical expression of 8-hydroxydeoxyguanosine (8-OHdG) in non-small cell carcinomas. Expression of 8-OHdG in nuclei of tumor cells. (A, B) Adenocarcinoma. (C, D) Squamous cell carcinoma.

  • Fig. 2. Kaplan-Meier survival analysis of non-small cell lung carcinoma patients. Overall survival in 203 patients according to the expression of 8-hydroxydeoxyguanosine (8-OHdG) (A), p53 (B), Ki-67 (C), smoking history (D), and T category (American Joint Committee on Cancer (AJCC) 8th edition) (E).


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