魏建昌　胡鹤　王强

[摘要] 目的 探究腦特异性新生血管抑制因子1（BAI1）在结直肠癌中的表达与结直肠癌患者临床病理学特征的关系。 方法 2016年5月～2017年7月，购买包含有208个结直肠癌和8个正常结肠组织及其临床信息的组织芯片。查询癌症基因组图谱数据库，内含192例结直肠癌患者的mRNA表达信息。通过免疫组化检测组织芯片正常结肠组织与结直肠癌组织中BAI1表达的情况，检测BAI1表达与结直肠癌患者临床病理特征的关系，采用Kaplan-Meier法和Log-rank秩检验方法进行生存曲线。最后使用Cox回归模型进行单变量分析和多变量分析，判断BAI1对预后的判断价值。 结果 BAI1在结直肠癌组织中的含量较正常组织显著上升（P < 0.001）。高BAI1表达与临床分期（P = 0.004）和肿瘤浸润（P = 0.006）相关。癌症基因组图谱（TCGA）中结直肠癌患者的BAI1 mRNA表达进一步提示了较晚的临床分期（P = 0.027）、较严重的肿瘤浸润（P = 0.021）的结直肠癌中BAI1表达水平更高。Kaplan-Meier生存曲线提示BAI1 mRNA高表达的患者比低表达水平的患者总生存期明显减少（P = 0.02）。BAI1 mRNA的高表达是结直肠癌预后的独立影响因素（HR = 2.895，95%CI：1.012～8.281，P = 0.047）。 结论 BAI1与结直肠癌的恶性相关。BAI1的高表达可能提示结直肠癌患者的不良预后。

[关键词] 脑特异性新生血管抑制因子1；结直肠癌；临床病理学特征；独立预后因素

[中图分类号] R442.8 [文献标识码] A [文章编号] 1673-7210（2018）07（b）-0008-04

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.

[Key words] Brain-specific angiogenesis inhibitor 1； Colorectal cancer； Clinicopathological features； Independent prognostic factor

结直肠癌（colorectal cancer，CRC）是一种常见的消化恶性肿瘤，在全球癌症相关死亡排名中排名第四[1]。目前虽然已经发现一些基因与CRC进展密切相关[2-3]，但是完整的分子机制仍是不确定。因此，有必要寻找新的标志物，并进一步阐明CRC的生物学特性，从而改善治疗效果，改善患者预后。

脑特异性血管生成抑制因子1（brain-specific angiogenesis inhibitor 1，BAI1）主要表达于人脑，位于细胞浆和细胞膜当中，当以基因转染的方式在培养细胞中表达时，主要表达在细胞膜上[4]，是黏附G蛋白偶联受体家族的一员[5]。作为一种膜蛋白，BAI1的胞外区域包含有5个TSP-1型重复序列和7个跨膜区域，由野生型p53诱导生成。其主要功能为抗血管生成[6-7]。几项研究表明，在包括肺腺癌[8]、胃癌[9]、胶质母细胞瘤[10-12]在内的几种癌症中，BAI1 mRNA表达水平下调了。……