Expression of RNF8 in breast cancer

Abstract

Background: Breast cancer is a heterogeneous disease and is the most frequent malignancy for female. Traditional prognostic markers currently in use encounter limitations. More prognostic and predictive markers would be useful to guide the selection of treatment and estimate the risks of patients. RNF8 is a 485 amino acid long nuclear protein which is known as a key protein involved in mediating double-strand breaks (DSBs)repair. As other regulatory proteins in DSBs, it may be a potential prognostic or predictive marker to guide future treatment in breast cancer. Materials and methods: This study investigated the expression of RNF8 in breast cancer by immunohistochemical (IHC) analysis using RNF8 antibody. Seventy-nine cases of breast cancer were analyzed using tissue microarray (TMA) and the RNF8 expression pattern was correlated with the age of patients’ first breast cancer diagnosis, tumor stage, tumor grade, lymph node involvement, status of hormone receptor such as estrogen receptor (ER) and progesterone receptor (PR), response to the adjuvant treatment such as tamoxifen, relapse and metastasis. Results: Our results showed statistically significant inverse correlation between total RNF8 with lymph node involvement, disease relapse, metastasis and tamoxifen resistance with p-values of 0.003, 0.011, 0.001 and 0.018 respectively. Furthermore, a trend of decreased survival (p= 0.058) in patients expressing lower level of total RNF8 in the breast cancer cells was observed using disease-specific survival analysis. Conclusion: Low RNF8 expression is associated with lymph node metastasis, local disease relapse, distant metastasis as well as with tamoxifen resistance. RNF8 might be potentially useful in predicting tamoxifen resistance and guide the use of adjuvant therapy. Future molecular functional study is needed to elucidate the role of RNF8 in the progression of breast cancer.