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

Abstract

Background: Oxidative 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.

Methods: Serum 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.

Results: In 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).

Conclusions: An 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.

Fig. 1

Association between EOC histology and serum 8-OHdG level (p = 0.033)

Fig. 2

Kaplan–Meier curves demonstrating relationships between serum 8-OHdG concentrations and disease-free survival in the whole study population (a), overall survival in the whole study population (b), disease-free survival in cases of carcinoma with endometrioid histology (c) and overall survival in the endometrioid histology group (d)