Department of Radiation Oncology, School of Medicine,Vanderbilt University, Nashville, TN, USA.
Pancreas. 2013 Aug;42(6):977-82. doi: 10.1097/MPA.0b013e318287885c.
The tumor-suppressor breast cancer susceptibility gene 1 (BRCA1) is a nuclear-cytoplasmic shuttling protein that when in the nucleus is required for DNA repair whereas when in the cytoplasm is important in activating cell death processes. Although BRCA1 mutations have been shown to be associated with an increased risk of pancreatic ductal adenocarcinoma (PDAC), its role in disease progression is yet to be determined. We hypothesized that BRCA1 expression pattern could be used as a prognostic biomarker.
Sixty-seven patients who underwent resections for PDAC were included. A tissue microarray was constructed, stained with antibodies to BRCA1, and scored for intensity and subcellular location. Univariate and multivariate statistical analyses were performed.
An increase in cytosolic BRCA1 distribution was associated with higher pathologic stage (P = 0.006). Nuclear-cytosolic BRCA1 distribution was associated with a decrease in recurrence-free survival with a hazards ratio of 1.4 (P = 0.059). Decreased BRCA1 intensity was associated with higher pathologic stage (P = 0.027), but BRCA1 intensity was not associated with overall survival or recurrence-free survival.
Our results demonstrate a possible association of BRCA1 expression pattern with pathologic stage, implying a potential role of BRCA1 in PDAC development and progression.
抑癌基因乳腺癌易感基因 1（BRCA1）是一种核质穿梭蛋白，当其位于核内时，是 DNA 修复所必需的；而当其位于细胞质中时，对于激活细胞死亡过程很重要。尽管已经表明 BRCA1 突变与胰腺导管腺癌（PDAC）的风险增加有关，但它在疾病进展中的作用尚未确定。我们假设 BRCA1 表达模式可用作预后生物标志物。
纳入 67 例接受 PDAC 切除术的患者。构建组织微阵列，用抗 BRCA1 抗体染色，并对强度和亚细胞定位进行评分。进行单变量和多变量统计分析。
细胞质中 BRCA1 分布的增加与较高的病理分期相关（P = 0.006）。核质 BRCA1 分布与无复发生存率降低相关，风险比为 1.4（P = 0.059）。BRCA1 强度降低与较高的病理分期相关（P = 0.027），但 BRCA1 强度与总生存率或无复发生存率无关。
我们的结果表明 BRCA1 表达模式与病理分期之间可能存在关联，这表明 BRCA1 可能在 PDAC 的发生和发展中起作用。
