Department of Radiation Oncology, The Cancer Institute of New Jersey and UMDNJ/Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA.
Cancer. 2012 Feb 15;118(4):888-98. doi: 10.1002/cncr.26352. Epub 2011 Jul 14.
DEAD box 1 (DDX1) is an RNA helicase with a number of roles, including translation initiation, RNA splicing and modification, and possibly DNA double-strand break repair. Amplification of DDX1 expression has been implicated in tumors including neuroblastoma, Wilms tumor, retinoblastoma, and testicular carcinoma. The purpose of this study was to evaluate the prognostic significance of DDX1 expression in patients with breast cancer treated with breast-conserving therapy.
Paraffin-embedded specimens from 282 women with node-negative stage 1 and 2 breast cancer treated with breast-conserving surgery and radiation therapy were constructed into tissue microarrays and stained for DDX1. The molecular profiles were correlated with clinicopathologic factors and overall, local, and distant metastatic-free survival.
DDX1 positivity was identified in 142 (50%) patients. The median age at diagnosis was 53 years. Eighty percent of the patients had T1 disease; 11% were HER2neu-positive, and 18% had triple-negative disease. DDX1 negativity was strongly associated with triple-negative phenotype (P = .01). DDX1 positivity was found to be associated with improved local relapse-free survival (96% vs 85%, P = .0233), distant metastatic-free survival (95% vs 85%, P = .0320), and overall survival (92% vs 84%, P = .0474) at 10 years.
Node-negative, early stage breast cancer patients with high levels of DDX1 were found to have a significant improvement in local control, distant metastatic-free survival, and overall survival compared with patients with low levels of DDX1.
DEAD 盒 1(DDX1)是一种 RNA 解旋酶,具有多种功能,包括翻译起始、RNA 剪接和修饰,以及可能的 DNA 双链断裂修复。DDX1 表达的扩增与包括神经母细胞瘤、Wilms 瘤、视网膜母细胞瘤和睾丸癌在内的肿瘤有关。本研究旨在评估 DDX1 表达在接受保乳治疗的乳腺癌患者中的预后意义。
构建了 282 例淋巴结阴性 1 期和 2 期乳腺癌患者的石蜡包埋标本组织微阵列,并对其进行 DDX1 染色。将分子谱与临床病理因素以及总生存、局部无复发生存和远处无转移生存相关联。
142 例(50%)患者为 DDX1 阳性。诊断时的中位年龄为 53 岁。80%的患者为 T1 疾病;11%为 HER2neu 阳性,18%为三阴性疾病。DDX1 阴性与三阴性表型密切相关(P=0.01)。DDX1 阳性与局部无复发生存(96% vs 85%,P=0.0233)、远处无转移生存(95% vs 85%,P=0.0320)和 10 年总生存(92% vs 84%,P=0.0474)的改善相关。
在淋巴结阴性、早期乳腺癌患者中,高水平的 DDX1 与局部控制、远处无转移生存和总生存的显著改善相关,而低水平的 DDX1 则与之相反。