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The significance of the alteration of 8-OHdG in serous ovarian carcinoma

BACKGROUND: Oxidative damage and DNA repair dysfunction are associated with carcinogenesis. 8-OHdG is one of the major oxidative DNA adducts. Present work aims to investigate whether the expression of 8-OHdG and its key repair gene hOGG1 play distinctive role in two types of serous ovarian cancer. M...

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Autores principales: Xu, Xia, Wang, Yan, Guo, Wenwen, Zhou, Yiqing, Lv, Chunmei, Chen, Xiaoxiang, Liu, Kaijiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875897/
https://www.ncbi.nlm.nih.gov/pubmed/24165045
http://dx.doi.org/10.1186/1757-2215-6-74
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author Xu, Xia
Wang, Yan
Guo, Wenwen
Zhou, Yiqing
Lv, Chunmei
Chen, Xiaoxiang
Liu, Kaijiang
author_facet Xu, Xia
Wang, Yan
Guo, Wenwen
Zhou, Yiqing
Lv, Chunmei
Chen, Xiaoxiang
Liu, Kaijiang
author_sort Xu, Xia
collection PubMed
description BACKGROUND: Oxidative damage and DNA repair dysfunction are associated with carcinogenesis. 8-OHdG is one of the major oxidative DNA adducts. Present work aims to investigate whether the expression of 8-OHdG and its key repair gene hOGG1 play distinctive role in two types of serous ovarian cancer. MATERIALS AND METHODS: 8-OHdG level in DNA from tumor and matched tumor-adjacent normal tissue in 48 high-grade papillary serous carcinomas (HG-SOC), 24 low-grade papillary serous carcinomas (LG-SOC), 20 serous cystadenomas, and 16 non-tumor control ovaries was tested. The Cox proportional hazards model and the log-rank test were used to assess the associations between the 8-OHdG level in two types of serous cancer and patients’ survival. Real-time polymerase chain reaction and protein immunoblot were employed to detect hOGG1 mRNA and protein levels in tumor and adjacent normal tissues. Immunohistochemistry was used to determine the expression of hOGG1 and p53. RESULTS: There was no difference of average 8-OHdG/10(6)dG DNA level either between HG-SOC (27.8 ± 8.9), LG-SOC (25.2 ± 7.4) and benign serous cystadenoma (26.5 ± 7.7, p = 0.35); or between the tumor-adjacent normal tissue of HG-SOC (18.8 ± 5.2), LG-SOC (21.4 ± 6.5), benign serous cystadenoma (20.5 ± 9.1) and non-tumor ovary (21.6 ± 4.9, p = 0.62). The 8-OHdG/10(6)dG level was significantly higher in tumor comparing to that in matched normal tissue adjacent to carcinoma in HG-SOC (1.52 ± 0.52, p = 0.02), but not in LG-SOC or benign serous cystadenoma. Increased level of 8-OHdG in tumor DNA was an independent factor of overall survival in serous ovarian carcinoma upon multivariate analysis (p < 0.01). Increased level of 8-OHdG in tumor DNA indicates poorer overall and progression-free survival durations than counterparts (47.3 vs 105.7 months and 13.5 vs 45.3 months, respectively). Protein levels of hOGG1 were remarkably decreased in HG-SOC (p < 0.01), but not in LG-SOC and serous cystadenoma compared with the tissue adjacent to carcinoma. A positive result on p53 immunostaining was associated with lower hOGG1 expression in HG-SOC (p = 0.04). CONCLUSION: Increased 8-OHdG level and decreased expression of hOGG1 in tumor were found in HG-SOC but not LG-SOC. Increased 8-OHdG level in tumor DNA was significantly associated with poorer overall survival and progression-free survival in serous ovarian carcinoma.
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spelling pubmed-38758972014-01-01 The significance of the alteration of 8-OHdG in serous ovarian carcinoma Xu, Xia Wang, Yan Guo, Wenwen Zhou, Yiqing Lv, Chunmei Chen, Xiaoxiang Liu, Kaijiang J Ovarian Res Research BACKGROUND: Oxidative damage and DNA repair dysfunction are associated with carcinogenesis. 8-OHdG is one of the major oxidative DNA adducts. Present work aims to investigate whether the expression of 8-OHdG and its key repair gene hOGG1 play distinctive role in two types of serous ovarian cancer. MATERIALS AND METHODS: 8-OHdG level in DNA from tumor and matched tumor-adjacent normal tissue in 48 high-grade papillary serous carcinomas (HG-SOC), 24 low-grade papillary serous carcinomas (LG-SOC), 20 serous cystadenomas, and 16 non-tumor control ovaries was tested. The Cox proportional hazards model and the log-rank test were used to assess the associations between the 8-OHdG level in two types of serous cancer and patients’ survival. Real-time polymerase chain reaction and protein immunoblot were employed to detect hOGG1 mRNA and protein levels in tumor and adjacent normal tissues. Immunohistochemistry was used to determine the expression of hOGG1 and p53. RESULTS: There was no difference of average 8-OHdG/10(6)dG DNA level either between HG-SOC (27.8 ± 8.9), LG-SOC (25.2 ± 7.4) and benign serous cystadenoma (26.5 ± 7.7, p = 0.35); or between the tumor-adjacent normal tissue of HG-SOC (18.8 ± 5.2), LG-SOC (21.4 ± 6.5), benign serous cystadenoma (20.5 ± 9.1) and non-tumor ovary (21.6 ± 4.9, p = 0.62). The 8-OHdG/10(6)dG level was significantly higher in tumor comparing to that in matched normal tissue adjacent to carcinoma in HG-SOC (1.52 ± 0.52, p = 0.02), but not in LG-SOC or benign serous cystadenoma. Increased level of 8-OHdG in tumor DNA was an independent factor of overall survival in serous ovarian carcinoma upon multivariate analysis (p < 0.01). Increased level of 8-OHdG in tumor DNA indicates poorer overall and progression-free survival durations than counterparts (47.3 vs 105.7 months and 13.5 vs 45.3 months, respectively). Protein levels of hOGG1 were remarkably decreased in HG-SOC (p < 0.01), but not in LG-SOC and serous cystadenoma compared with the tissue adjacent to carcinoma. A positive result on p53 immunostaining was associated with lower hOGG1 expression in HG-SOC (p = 0.04). CONCLUSION: Increased 8-OHdG level and decreased expression of hOGG1 in tumor were found in HG-SOC but not LG-SOC. Increased 8-OHdG level in tumor DNA was significantly associated with poorer overall survival and progression-free survival in serous ovarian carcinoma. BioMed Central 2013-10-29 /pmc/articles/PMC3875897/ /pubmed/24165045 http://dx.doi.org/10.1186/1757-2215-6-74 Text en Copyright © 2013 Xu et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Xu, Xia
Wang, Yan
Guo, Wenwen
Zhou, Yiqing
Lv, Chunmei
Chen, Xiaoxiang
Liu, Kaijiang
The significance of the alteration of 8-OHdG in serous ovarian carcinoma
title The significance of the alteration of 8-OHdG in serous ovarian carcinoma
title_full The significance of the alteration of 8-OHdG in serous ovarian carcinoma
title_fullStr The significance of the alteration of 8-OHdG in serous ovarian carcinoma
title_full_unstemmed The significance of the alteration of 8-OHdG in serous ovarian carcinoma
title_short The significance of the alteration of 8-OHdG in serous ovarian carcinoma
title_sort significance of the alteration of 8-ohdg in serous ovarian carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875897/
https://www.ncbi.nlm.nih.gov/pubmed/24165045
http://dx.doi.org/10.1186/1757-2215-6-74
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