Laboratório de Citogenética Humana e Oncogenética, Departamento de Genética, UFPR, Curitiba, Paraná, Brazil.
PLoS One. 2013 Jun 25;8(6):e66243. doi: 10.1371/journal.pone.0066243. Print 2013.
DNA repair is a key determinant in the cellular response to therapy and tumor repair status could play an important role in tailoring patient therapy. Our goal was to evaluate the mRNA of 13 genes involved in different DNA repair pathways (base excision, nucleotide excision, homologous recombination, and Fanconi anemia) in paraffin embedded samples of triple negative breast cancer (TNBC) compared to luminal A breast cancer (LABC). Most of the genes involved in nucleotide excision repair and Fanconi Anemia pathways, and CHK1 gene were significantly less expressed in TNBC than in LABC. PARP1 levels were higher in TNBC than in LABC. In univariate analysis high level of FANCA correlated with an increased overall survival and event free survival in TNBC; however multivariate analyses using Cox regression did not confirm FANCA as independent prognostic factor. These data support the evidence that TNBCs compared to LABCs harbour DNA repair defects.
DNA 修复是细胞对治疗反应的关键决定因素,肿瘤修复状态可能在制定患者治疗方案方面发挥重要作用。我们的目标是评估 13 个参与不同 DNA 修复途径(碱基切除、核苷酸切除、同源重组和范可尼贫血)的基因在三阴性乳腺癌(TNBC)与管腔 A 型乳腺癌(LABC)石蜡包埋样本中的 mRNA 表达。与 LABC 相比,参与核苷酸切除修复和范可尼贫血途径的大多数基因以及 CHK1 基因在 TNBC 中的表达明显较低。PARP1 水平在 TNBC 中高于 LABC。在单因素分析中,高水平的 FANCA 与 TNBC 的总生存期和无事件生存期增加相关;然而,使用 Cox 回归的多因素分析并未证实 FANCA 是独立的预后因素。这些数据支持了以下证据,即与 LABC 相比,TNBC 存在 DNA 修复缺陷。