The prognostic significance of Jun transcription factors in ovarian cancer

Abstract

The Jun proteins (c-Jun, JunD and JunB) play an important role in the regulation of cell proliferation, apoptosis and angiogenesis. It is well established that these proteins participate in the carcinogenesis and progression in several tumour types. However, little is known about the prognostic significance of Jun proteins in patients with invasive epithelial ovarian carcinoma. We analysed fresh-frozen tissues of 161 ovarian cancer patients by using Western blot analysis to investigate protein levels of JunB, JunD, c-Jun and phosphorylated c-Jun (pc-Jun Ser63). The results were correlated with clinicopathologic prognostic parameters and survival data. A high pc-Jun expression was significantly associated with shorter progression-free survival (14 vs. 16 months, p = 0.017) and overall survival (25 vs. 41 months, p = 0.038). In case of JunD, moderate protein levels were associated with a better prognosis, leading to longer progression-free and overall survival compared to weak or strong JunD expression (PFS in cases with weak/moderate/strong JunD expression: 14 vs. 19.5 vs. 16 months, p = 0.011; OAS: 32 vs. 42 vs. 35.5 months, p = 0.009). Multivariate Cox regression analysis confirmed an independent and significant impact of pc-Jun and JunD on the patient's prognosis. Our results show that Jun proteins (pc-Jun and JunD) influence carcinogenesis and tumour progression, suggesting a significant role as prognostic predictors in human ovarian carcinoma.