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HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of  HJURP  in breast cancer and its correlation with radiotherapeutic outcome.    Methods  We measured  HJURP  expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis.    Results   HJURP  was expressed at higher level in breast cancer than in normal breast tissue.  HJURP  mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher  HJURP  mRNA levels significantly decreased disease-free and overall survival.  HJURP  mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates,  HJURP  mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition  HJURP  mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high  HJURP  expression were validated in five additional breast cancer cohorts. Furthermore, the patients with high  HJURP  levels were much more sensitive to radiotherapy.  In vitro  studies in breast cancer cell lines showed that cells with high  HJURP  levels were more sensitive to radiation treatment and had a higher rate of apoptosis than those with low levels. Knock down of  HJURP  in human breast cancer cells using shRNA reduced the sensitivity to radiation treatment.  HJURP  mRNA levels were significantly correlated with CENPA mRNA levels.    Conclusions   HJURP  mRNA level is a prognostic factor for disease-free and overall survival in patients with breast cancer and is a predictive biomarker for sensitivity to radiotherapy.

The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer