Department of Mathematics, University of Texas Arlington, Arlington, Texas, United States of America.
Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.
PLoS One. 2019 Feb 4;14(2):e0211507. doi: 10.1371/journal.pone.0211507. eCollection 2019.
BAP1 is a tumor suppressor gene important to the development and prognosis of many cancers, especially uveal melanoma (UM). Its role in more common cancers such as breast and colon cancer is largely unknown. We collected the transcriptome profiling data sets from the TCGA uveal melanoma (TCGA-UVM), breast cancer (TCGA-BRCA), and colon cancer (TCGA-COAD) projects to analyze the expression of BAP1. We found that patients with UM and breast cancer, but not colon cancer, who died had a lower level of BAP1 gene expression compared to surviving patients. Importantly, in breast cancer patients, the lowest BAP1 expression levels corresponded to the dead young patients (age at diagnosis < 46). Since the number of cases in TCGA-BRCA was much higher than TCGA-UVM, we obtained highly correlated genes with BAP1 in invasive breast carcinomas. Then, we tested if these genes are also highly correlated with BAP1 in UM and colon cancer. We found that BAP1 is highly positively correlated with RBM15B and USP19 expression in invasive breast carcinoma, UM, and colon adenocarcinoma. All three genes are located in close proximity on the 3p21 tumor suppressor region that is commonly altered in many cancers.
BAP1 是一个重要的抑癌基因,对许多癌症的发生和预后都有重要作用,尤其是葡萄膜黑色素瘤(UM)。其在乳腺癌和结肠癌等更常见癌症中的作用尚不清楚。我们收集了来自 TCGA 葡萄膜黑色素瘤(TCGA-UVM)、乳腺癌(TCGA-BRCA)和结肠癌(TCGA-COAD)项目的转录组谱数据,以分析 BAP1 的表达。我们发现,与存活患者相比,死于 UM 和乳腺癌的患者(诊断时年龄<46 岁)的 BAP1 基因表达水平较低。重要的是,在乳腺癌患者中,BAP1 表达水平最低的是死亡的年轻患者。由于 TCGA-BRCA 中的病例数远高于 TCGA-UVM,我们获得了与乳腺癌浸润性癌中 BAP1 高度相关的基因。然后,我们测试了这些基因在 UM 和结肠癌中是否也与 BAP1 高度相关。我们发现,在乳腺癌浸润性癌、UM 和结肠腺癌中,BAP1 与 RBM15B 和 USP19 的表达呈高度正相关。这三个基因都位于 3p21 肿瘤抑制区域附近,该区域在许多癌症中经常发生改变。