Preoperative serum 8-hydroxydeoxyguanosine is associated with chemoresistance and is a powerful prognostic factor in endometrioid-type epithelial ovarian cancer.

Marjo Pylväs-Eerola,Peeter Karihtala,Ulla Puistola

doi:10.1186/s12885-015-1504-6

Marjo Pylväs-Eerola, Peeter Karihtala + Show 1 more

Open Access

https://doi.org/10.1186/s12885-015-1504-6

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Journal: BMC cancer	Publication Date: Jul 2, 2015
Citations: 53	License type: CC BY 4.0

Affiliation: Oulu University Hospital, University of Oulu

Abstract

BackgroundOxidative stress is a widely seen phenomenon in several carcinomas. Increasing evidence also suggests that it has a significant role in the development of epithelial ovarian carcinoma (EOC). 8-Hydroxydeoxyguanosine (8-OHdG) is one of the main indicators of oxidative stress and increased expression of 8-OHdG has previously been seen in EOC. DJ-1 is an oncoprotein connected to oxidative stress regulation, but its role in ovarian cancer is not well known. We investigated redox status in different histotypes of EOC by measuring serum 8-OHdG and DJ-1 concentrations and their associations with known prognostic factors.MethodsSerum samples from newly diagnosed EOC patients were collected in 1996–2009 and stored at the Department of Obstetrics and Gynecology, Oulu University Hospital. Serum 8-OHdG and DJ-1 levels were measured by using commercially available ELISA kits. Clinical data was gathered retrospectively from the patients` files. Results were analyzed by using SPSS software.ResultsIn total, 112 patient samples were analyzed (38 serous, 20 mucinous, 34 endometrioid and 20 clear-cell). High serum 8-OHdG levels were associated with poor overall survival (OS) (p = 0.019), poor disease-free survival (DFS) (p = 0.020), platinum resistance (p = 0.002), serous histology versus other (p = 0.033), stage III–IV versus I–II (p = 0.009) and suboptimal surgical outcome (p = 0.012). Regarding histotypes, in the endometrioid EOC group in particular, serum 8-OHdG levels were significantly associated with poor DFS (p = 0.005), suboptimal surgical outcome (p = 0.025), and platinum resistance (p = 0.007). The prognostic significance of 8-OHdG in patients with endometrioid cancer in terms of DFS was confirmed in Cox regression analysis. High DJ-1 levels were associated with high histological grade (p = 0.029) and nonsignificantly associated with serous histology vs. other histology (p = 0.089).ConclusionsAn elevated serum 8-OHdG level is a significant predictor of poor prognosis, especially in cases of the endometrioid subtype of ovarian carcinoma. High 8-OHdG levels are associated with all traditional factors of poor prognosis in ovarian cancer and they also predict earlier development of platinum resistance. These results could be valuable when deciding the primary treatment mode for EOC patients.

Highlights

Oxidative stress is a widely seen phenomenon in several carcinomas
Ovulation creates a void on the ovarian surface, which leads to the wound-healing process, with increased levels of inflammatory mediators and reactive oxygen species (ROS) [1,2,3]
We have previously reported that high serum and tumor tissue levels of 8-OHdG in epithelial ovarian carcinoma (EOC) patients are associated with traditional factors of poor prognosis and with serous histology [26]

Summary

Introduction

Oxidative stress is a widely seen phenomenon in several carcinomas. Increasing evidence suggests that it has a significant role in the development of epithelial ovarian carcinoma (EOC). 8-Hydroxydeoxyguanosine (8-OHdG) is one of the main indicators of oxidative stress and increased expression of 8-OHdG has previously been seen in EOC. Increasing evidence suggests that it has a significant role in the development of epithelial ovarian carcinoma (EOC). 8-Hydroxydeoxyguanosine (8-OHdG) is one of the main indicators of oxidative stress and increased expression of 8-OHdG has previously been seen in EOC. DJ-1 is an oncoprotein connected to oxidative stress regulation, but its role in ovarian cancer is not well known. Ovarian cancer is the seventh most common cancer worldwide and one of the main causes of cancer-related death. It is diagnosed at an advanced stage when the prognosis is poor. In recent years many studies have shown the role of oxidative stress in the development of ovarian and other cancers. It has been suggested that cancer cells from the fallopian tubes, the cervix or endometriotic lesions migrate to the ovaries and form tumors near the corpus luteum [5]

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