Stahl David, Braun Martin, Gentles Andrew J, Lingohr Philipp, Walter Adeline, Kristiansen Glen, Gütgemann Ines
Institute of Pathology, University Hospital Bonn, Bonn, Germany.
Center for Cancer Systems Biology (CCSB), Stanford University, Stanford, California, USA.
Oncotarget. 2017 Jul 18;8(44):76329-76339. doi: 10.18632/oncotarget.19357. eCollection 2017 Sep 29.
Gastric adenocarcinomas are associated with a poor prognosis due to the fact that the tumor has often metastasized by the time of diagnosis and prognostic markers are urgently needed to tailor treatment. We examined the expression of the mitotic spindle checkpoint protein BUB1 (budding uninhibited by benzimidazoles 1) and Ki-67 protein expression by immunohistochemistry in 218 patients with primary gastric adenocarcinomas. Tumors with low frequency of BUB1 expression were associated with larger tumor size (pT) (p < 0.001), higher incidence of lymph node metastases (pN) (p = 0.027), distant metastases (pM) (p = 0.006) and higher UICC stage (p < 0.001). Furthermore, BUB1 expression was inversely correlated with residual tumor stage (p = 0.038). Abundant BUB1 protein expression correlated with frequent Ki-67 protein expression (p < 0.001) and low BUB1 expression was associated with shorter survival (p < 0.001). Univariate and multivariate analyses confirmed BUB1 to be an independent prognostic marker in gastric cancer (p = 0.021).
胃腺癌的预后较差,因为在诊断时肿瘤往往已经发生转移,因此迫切需要预后标志物来指导治疗。我们通过免疫组织化学检测了218例原发性胃腺癌患者有丝分裂纺锤体检查点蛋白BUB1(苯并咪唑不抑制的芽殖1)的表达以及Ki-67蛋白的表达。BUB1表达频率低的肿瘤与更大的肿瘤大小(pT)相关(p<0.001),淋巴结转移(pN)发生率更高(p = 0.027),远处转移(pM)发生率更高(p = 0.006)以及更高的国际抗癌联盟(UICC)分期(p<0.001)。此外,BUB1表达与残余肿瘤分期呈负相关(p = 0.038)。丰富的BUB1蛋白表达与频繁的Ki-67蛋白表达相关(p<0.001),而低BUB1表达与较短的生存期相关(p<0.001)。单因素和多因素分析证实BUB1是胃癌的独立预后标志物(p = 0.021)。