title: High RAD54B expression: an independent predictor of postoperative distant recurrence in colorectal cancer patients.
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.
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Nagai
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Yasuhara
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hata
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishikawa
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Tanaka
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Tomomichi
authors.initials: T
authors.lastname: Kiyomatsu
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Kawai
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nozawa
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Kazama
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ishihara
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Sunami
authors.affiliation: Department of Biostatistics, Graduate School of Medicine, Yokohama City University, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Yamanaka
authors.affiliation: Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Miyagawa
authors.affiliation: Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009687:Nuclear Proteins / Q000378:metabolism*; D011184:Postoperative Period; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018076:DNA, Complementary; D009687:Nuclear Proteins; C491221:RAD54B protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004265:DNA Helicases
keywords: RAD54B; colorectal cancer; distant recurrence; homologous recombination; prognosis