Expression of brain-specific angiogenesis inhibitor 1 in colorectal cancer and its correlations with clinicopathological features of colorectal cancer patients
WEI Jianchang* HU He* WANG Qiang CHEN Zhuanpeng YANG Ping ZHANG Tong CAO Jie
Digestive Disease Center, the First People′s Hospital of Guangzhou City, Guangzhou Medical University, Guangdong Province, Guangzhou 510180, China
Abstract:Objective To explore the roles of brain-specific angiogenesis inhibitor 1 in colorectal cancer and its correlations with clinicopathological features and prognosis of CRC patients. Methods Fom May 2016 to July 2017, tissue microarray with 208 CRC, 8 normal colon tissues and the clinical information was purchased. The cancer genome atlas (TCGA) dataset is a publicly available dataset with 192 primary CRC patients and the mRNA expressions. BAI1 in TMA of CRC and benign glandular epithelium cells was checked by immunohistochemistry. The exlpore the connection between the express of brain-specific angiogenesis inhibitor 1 with clinicopathological features. Overall survival curve was analyzed by Kaplan-Meier method and Log-rank test. Univariate analysis and multivariate analyses were analyzed with Cox proportional hazards regression to assess the prognostic value of high BAI1 expression for CRC patients. Results BAI1 was localized in the cytoplasm of CRC and benign glandular epithelium cells, showing higher protein levels in CRC tissues compared with normal colon samples (P < 0.001). High BAI1 protein expression was associated with high pathological grade (P = 0.039), advanced clinical stage (P = 0.004) and enhanced tumor invasion (P = 0.006). The cancer genome atlas (TCGA) mRNA expression further showed that BAI1 was upregulated in CRC with advanced clinical stage (P = 0.027) and enhanced tumor invasion (P = 0.021). Kaplan-Meier survival curves revealed that CRC patients with higher BAI1 mRNA levels had shorter overall survival than those with lower expression (P = 0.02). High BAI1 mRNA expression was an independent influence of factor for prognosis of CRC (HR = 2.895; 95%CI: 1.012-8.281; P = 0.047). Conclusion BAI1 ralates to aggressive CRC. High BAI1 expression may predict poor prognosis of CRC patients.
魏建昌* 胡鹤* 王强 陈转鹏 杨平 张通 曹杰. 脑特异性新生血管抑制因子1在结直肠癌中的表达及其与结直肠癌患者临床病理学特征的关系[J]. 中国医药导报, 2018, 15(20): 8-11.
WEI Jianchang* HU He* WANG Qiang CHEN Zhuanpeng YANG Ping ZHANG Tong CAO Jie. Expression of brain-specific angiogenesis inhibitor 1 in colorectal cancer and its correlations with clinicopathological features of colorectal cancer patients. 中国医药导报, 2018, 15(20): 8-11.
[1] Torre LA,Bray F,Siegel RL,et al. Global cancer statistics,2012 [J]. CA Cancer J Clin,2015,65(2):87-108 .
[2] Yang P,Wei J,Li W,et al. High expression of growth factor receptor-bound protein 14 predicts poor prognosis for colorectal cancer patients [M]. Biotechnol Lett,2016,38(6):1043-1047.
[3] He F,Chen H,Yang P,et al. Gankyrin sustains PI3K/GSK-3β/β-catenin signal activation and promotes colorectal cancer aggressiveness and progression [J]. Oncotarget,2016, 7(49):81 156-81 171.
[4] Mori K,Kanemura Y,Fujikawa H,et al. Brain-specific angiogenesis inhibitor 1(BAI1)is expressed in human cerebral neuronal cells [J]. Neurosci Res,2002,43(1):69-74.
[5] Cork SM,Van Meir EG. Emerging roles for the BAI1 protein family in the regulation of phagocytosis,synaptogenesis,neurovasculature,and tumor development [J].J Mol Medi,2011,89(8):743-752.
[6] Nishimori H,Shiratsuchi T,Urano T,et al. A novel brain-specific p53-target gene,BAI1,containing thrombospondin type 1 repeats inhibits experimental angiogenesis [J]. Oncogene,1997,15(18):2145-2150.
[7] Nishizaki M,Fujiwara T,Tanida T,et al. Recombinant adenovirus expressing wildtypep53 is antiangiogenic:a proposed mechanism forbystander effect [J]. Clin Cancer Res,1999,5(5):1015-1023.
[8] Hatanaka H,Oshika Y,Abe Y,et al. Vascularization is decreased in pulmonary adenocarcinomaexpressing brain-specific angiogenesis inhibitor 1 (BAI1) [J]. Int J Mol Med,2000,5(2):181-183.
[9] Miyamoto N,Yamamoto H,Taniguchi H,et al. Differential expression of angiogenesis-related genes in human gastric cancers with and those without high-frequency microsatellite instability [J]. Cancer Lett,2007,254(1):42-53.
[10] Kaur B,Brat DJ,Calkins CC,et al. Brain angiogenesis inhibitor 1 is differentially expressed in normal brain and glioblastoma independently of p53 expression [J]. Am J Pathol,2003,162(1):19-27.
[11] Nam DH,Park K,Suh YL,et al. Expression of VEGF and brain specific angiogenesis inhibitor-1 in glioblastoma:prognostic significance [J]. Oncol Rep,2004,11(4):863-869.
[12] Kang X,Xiao X,Harata M,et al. Antiangiogenic activity of BAI1 in vivo:implications for gene therapy of human glioblastomas [J]. Cancer Gene Ther,2006,13(4):385-392.
[13] Izutsu T,Konda R,Sugimura J,et al. Brain-Specific Angiogenesis Inhibitor 1 is a Putative Factor for Inhibition of Neovascular Formation in Renal Cell Carcinoma [J]. J Urol,2011,185(6):2353-2358.
[14] Kudo S,Konda R,Obara W,et al. Inhibition of tumor growth through suppression of angiogenesis by brain-specific angiogenesis inhibitor 1 gene transfer in murine renal cell carcinoma [J]. Oncol Rep,2007,18(4):785-791.
[15] Meisen WH,Dubin S,Sizemore ST,et al. Changes in BAI1 and Nestin expression are prognostic indicators for survival and metastases in Breast Cancer and Provide Opportunities for Dual Targeted Therapies [J]. Mol Cancer Ther,2015,14(1):307-314.
[16] Van Meir EG,Polverini PJ,Chazin VR,et al. Release of aninhibitor of angiogenesis upon induction of wild type p53 expression in glioblastoma cells [J]. Nat Genet,1994, 8(2):171-176.
[17] Monk KR,Naylor SG,Glenn TD,et al. A G protein-coupled receptor is essential for Schwann cells to initiate myelination [J]. Science,2009,325(5946):1402-11405.
[18] Sherman DL,Brophy PJ. Mechanisms of axon ensheathment and myelin growth [J]. Nat Rev Neurosci,2005,6(9):683-690.
[19] Fukushima Y,Oshika Y,Tsuchida T,et al. Brain-specific angiogenesis inhibitor 1 expression is inverselycorrelated with vascularity and distant metastasis of colorectal cancer [J]. Int J Oncol,1998,13(5):967-970.
[20] Yoshida Y,Oshika Y,Fukushima Y,et al. Expression of angiostatic factors in colorectal cancer [J]. Int J Oncol,1999, 15(6):1221-1225.