Overexpression of Transmembrane Protein BST2 is Associated with Poor Survival of Patients with Esophageal, Gastric, or Colorectal Cancer
Overexpression of Transmembrane Protein BST2 is Associated with Poor Survival of Patients with Esophageal, Gastric, or Colorectal Cancer
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DOI：
10.1245/s10434-016-5100-z
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发表时间：
2017-02-01
影响因子：
3.7
通讯作者：
Yasui, Wataru
中科院分区：
文献类型：
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作者：
Mukai, Shoichiro;Oue, Naohide;Yasui, Wataru
胃肠道（GI）癌，包括胃癌（GC）、结直肠癌（CRC）和食管鳞状细胞癌（ESCC），是全世界最常见的恶性肿瘤。为了鉴定编码胃肠癌中存在的跨膜蛋白的基因，从 MKN-74 GC 细胞中生成了大肠杆菌氨苄青霉素分泌陷阱文库，并确定 BST2 在 GC 中过度表达。本研究分析了BST2基因在人类胃肠道癌症中的表达和功能，并探讨了骨髓基质抗原2（BST-2）表达与胃肠道患者临床病理特征之间的关系。通过免疫组化方法分析了180例胃癌、140例结直肠癌和132例食管鳞癌中BST-2蛋白的表达和分布。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 法分析细胞生长情况。GC 组织中 BST-2 的免疫组织化学分析显示，180 例 GC 病例中有 65 例 (36%) BST-2 呈阳性。单变量和多变量分析表明，BST-2 表达是 GC 患者的独立预后分类指标。免疫组织化学分析显示，140 例 CRC 病例中 46% 和 132 例 ESCC 病例中 27% BST-2 呈阳性。在 ESCC 中，BST-2 表达是生存的独立预后预测因子。 BST2小干扰RNA (siRNA)转染的GC细胞的生长明显慢于阴性对照siRNA转染的GC细胞的生长。转染 BST2 siRNA 的 GC 细胞中磷酸化表皮生长因子受体、细胞外信号调节激酶和 Akt 的水平低于对照细胞。结果表明，BST-2 参与肿瘤进展，并可作为 GC 患者的独立预后分类器。由于 BST-2 在细胞膜上表达，因此 BST-2 可能成为 GC、CRC 和 ESCC 的治疗靶点。
Gastrointestinal (GI) cancer, including gastric cancer (GC), colorectal cancer (CRC), and esophageal squamous cell carcinoma (ESCC), is the most common malignancy worldwide. To identify genes that encode transmembrane proteins present in GI cancer, Escherichia coli ampicillin secretion trap libraries were generated from MKN-74 GC cells, and BST2 was identified as overexpressed in GC. This study analyzed the expression and function of the BST2 gene in human GI cancers and examined the relationship between bone marrow stromal antigen-2 (BST-2) expression and GI patient clinicopathologic characteristics.Expression and distribution of BST-2 protein was analyzed by immunohistochemistry in 180 GC cases, 140 CRC cases, and 132 ESCC cases. Cell growth was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.Immunohistochemical analysis of BST-2 in GC tissues showed that 65 (36 %) of 180 GC cases were positive for BST-2. Uni- and multivariate analyses demonstrated that BST-2 expression is an independent prognostic classifier of GC patients. Immunohistochemical analysis showed that 46 % of 140 CRC cases and 27 % of 132 ESCC cases were positive for BST-2. In ESCC, BST-2 expression was an independent prognostic predictor for survival. The growth of BST2 small interfering RNA (siRNA)-transfected GC cells was significantly slower than the growth of negative control siRNA-transfected GC cells. The levels of phosphorylated epidermal growth factor receptor, extracellular signal-regulated kinase, and Akt were lower in BST2 siRNA-transfected GC cells than in control cells.The results suggest that BST-2 is involved in tumor progression and serves as an independent prognostic classifier for patients with GC. Because BST-2 is expressed on the cell membrane, BST-2 could be a therapeutic target for GC, CRC, and ESCC.