High RAD54B expression: an independent predictor of postoperative distant recurrence in colorectal cancer patients.
High RAD54B expression: an independent predictor of postoperative distant recurrence in colorectal cancer patients.
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DOI：
10.18632/oncotarget.4222
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发表时间：
2015-08-28
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影响因子：
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通讯作者：
Watanabe T
中科院分区：
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作者：
Nagai Y;Yamamoto Y;Yasuhara T;Hata K;Nishikawa T;Tanaka T;Tanaka J;Kiyomatsu T;Kawai K;Nozawa H;Kazama S;Yamaguchi H;Ishihara S;Sunami E;Yamanaka T;Miyagawa K;Watanabe T
我们最近报道了一种特异的机制，即在同源重组中起重要作用的RAD 54 B通过在体外降解p53蛋白而促进基因组不稳定性。然而，RAD 54在结直肠癌（CRC）中的临床意义尚不清楚。因此，我们分析了RAD 54 B基因在CRC患者中的表达。使用训练集（n = 123），确定分层的最佳截止值，并在另一个队列（n = 89）中进行验证。Kaplan-Meier曲线显示，在训练集（P = 0.0013）和验证集（P = 0.024）中，与低表达组相比，RAD 54 B高表达组的无远处复发生存率显著更低。使用考克斯比例风险模型的多变量分析显示，在训练集（风险比，4.31; 95%CI，1.53-13.1; P = 0.0060）和验证集（风险比，3.63; 95%CI，1.23-10.7; P = 0.021）中，高RAD 54 B表达是独立预测因子。此外，部分证实了RAD 54 B与p53的靶基因CDKN 1A之间的负显著相关性，表明RAD 54 B即使在临床样品中也通过降解p53蛋白发挥作用。这项研究首次证明了RAD 54 B表达有可能作为一种新的预后生物标志物，特别是对于CRC患者的远处复发。
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.