# BRCC3 acts as a prognostic marker in nasopharyngeal carcinoma patients treated with radiotherapy and mediates radiation resistance in vitro

## TL;DR

High BRCC3 levels in nasopharyngeal cancer patients are linked to worse survival and radioresistance, suggesting it could be a useful biomarker and treatment target.

## Contribution

This study identifies BRCC3 as a novel prognostic marker and radiosensitivity mediator in nasopharyngeal carcinoma.

## Key findings

- High BRCC3 expression correlates with poor overall and relapse-free survival in patients.
- BRCC3 knockdown reduces radioresistance and impairs DNA repair in cancer cells.
- BRCC3 is an independent prognostic factor for nasopharyngeal carcinoma outcomes.

## Abstract

BRCC3 has been found to be aberrantly expressed in breast tumors and involved in DNA damage response. The contribution of BRCC3 to nasopharyngeal carcinoma prognosis and radiosensitivity is still unclear.

Immunohistochemical analysis of BRCC3 was carried out in 100 nasopharyngeal carcinoma tissues, and the protein level was correlated to patient survival. BRCC3 expression of nasopharyngeal carcinoma cell lines was determined by Western-blotting and real-time PCR. Additionally, the effects of BRCC3 knockdown on nasopharyngeal carcinoma cell clongenic survival, DNA damage repair, and cell cycle distribution after irradiation was assessed.

The BRCC3 protein level was inversely correlated with nasopharyngeal carcinoma patient overall survival (P < 0.001) and 3-year loco-regional relapse-free survival (P = 0.034). Multivariate analysis demonstrated that BRCC3 expression was an independent prognostic factor (P = 0.010). The expression of BRCC3 was much higher in radioresistant nasopharyngeal carcinoma cells than in radiosensitive cells. Knockdown of BRCC3 increased the cell survival fraction, attenuated DNA damage repair and resulted in G2/M cell cycle arrest in radioresistant NPC cells.

High BRCC3 expression in nasopharyngeal carcinoma patients is associated with poor survival. BRCC3 knockdown could abate the radioresistance in nasopharyngeal carcinoma cells. These findings suggest the utility of BRCC3 as a prognostic biomarker and novel target for nasopharyngeal carcinoma.