Oncotarget

Research Papers:

High RAD54B expression: an independent predictor of postoperative distant recurrence in colorectal cancer patients

Yuzo Nagai, Yoko Yamamoto, Takaaki Yasuhara, Keisuke Hata, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Hiroaki Nozawa, Shinsuke Kazama, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Takeharu Yamanaka, Kiyoshi Miyagawa and Toshiaki Watanabe _

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Oncotarget. 2015; 6:21064-21073. https://doi.org/10.18632/oncotarget.4222

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Abstract

Yuzo Nagai1, Yoko Yamamoto1, Takaaki Yasuhara2, Keisuke Hata1, Takeshi Nishikawa1, Toshiaki Tanaka1, Junichiro Tanaka1, Tomomichi Kiyomatsu1, Kazushige Kawai1, Hiroaki Nozawa1, Shinsuke Kazama1, Hironori Yamaguchi1, Soichiro Ishihara1, Eiji Sunami1, Takeharu Yamanaka3, Kiyoshi Miyagawa2 and Toshiaki Watanabe1

1 Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan

2 Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan

3 Department of Biostatistics, Graduate School of Medicine, Yokohama City University, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, Japan

Correspondence to:

Toshiaki Watanabe, email:

Keywords: RAD54B, colorectal cancer, homologous recombination, prognosis, distant recurrence

Received: April 21, 2015 Accepted: May 09, 2015 Published: May 20, 2015

Abstract

We recently reported a specific mechanism that RAD54B, an important factor in homologous recombination, promotes genomic instability via the degradation of p53 protein in vitro. However, clinical significance of RAD54Bin colorectal cancer (CRC) remains unclear. Thus we analyzed RAD54B geneexpression in CRC patients. Using the training set (n = 123), the optimal cut-off value for stratification was determined, and validated in another cohort (n = 89). Kaplan–Meier plots showed that distant recurrence free survival was significantly lesser in high RAD54B expression group compared with that of low expression group in both training (P = 0.0013) and validation (P = 0.024) set. Multivariate analysis using Cox proportional-hazards model showed that high RAD54B expression was an independent predictor in both training (hazard ratio, 4.31; 95% CI, 1.53–13.1; P = 0.0060) and validation (hazard ratio, 3.63; 95% CI, 1.23–10.7; P = 0.021) set. In addition, a negative significant correlation between RAD54B and CDKN1A, a target gene of p53, was partially confirmed, suggesting that RAD54B functions via the degradation of p53 protein even in clinical samples. This study first demonstrated RAD54B expression has potential to serve as a novel prognostic biomarker, particularly for distant recurrence in CRC patients.


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