Zeng Changqing, Feng Xingyu, Wang Wei, Lv Lin, Fang Cheng, Chi Liangjie, Huang Liangxiang, Zhou Zhiwei
Department of Gastric Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
Department of Gastrointestinal Surgery, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.
Oncol Lett. 2017 Jun;13(6):4161-4168. doi: 10.3892/ol.2017.5993. Epub 2017 Apr 5.
The present study aimed to investigate the expression and prognostic significance of insulin-like growth factor binding protein 6 (IGFBP-6) in gastric adenocarcinoma. The expression of IGFBP-6 was examined in 263 specimens from gastric adenocarcinoma patients using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemical (IHC) staining. The association between IGFBP-6 expression, clinicopathological factors and clinical outcomes was investigated. Akaike information criterion (AIC) and Harrell's concordance index (c-index) were used to evaluate the accuracy of the predictive prognosis. RT-qPCR and western blotting results showed that IGFBP-6 mRNA expression was lower in the tumors compared with that in adjacent non-tumor tissues. IGFBP-6 showed significantly decreased expression in 170 out of 263 patients based on IHC data and this was associated with a larger tumor size (P<0.001) and poorly-differentiated adenocarcinoma (P=0.001), as well as with palliative gastrectomy (P=0.015). Additionally, decreased expression of IGFBP-6 was associated with stage T3/4a/4b disease and lymph node-positive metastasis (P<0.001). The association between decreased expression and a poor prognosis was revealed by Kaplan-Meier curves. Cox regression model identified IGFBP-6 as an independent prognostic factor. The prognostic value of the model with IGFBP-6 expression (AIC, 924.881; c-index, 0.878) was superior to that without IGFBP-6 expression (AIC, 947.164; c-index, 0.825). In conclusion, IGFBP-6 involves the development and progression of gastric adenocarcinoma, and its decreased expression predicts poor clinical outcomes.
本研究旨在探讨胰岛素样生长因子结合蛋白6(IGFBP-6)在胃腺癌中的表达及其预后意义。采用逆转录定量聚合酶链反应(RT-qPCR)、蛋白质免疫印迹法和免疫组织化学(IHC)染色检测263例胃腺癌患者标本中IGFBP-6的表达。研究IGFBP-6表达与临床病理因素及临床结局之间的关联。使用赤池信息准则(AIC)和哈雷尔一致性指数(c指数)评估预测预后的准确性。RT-qPCR和蛋白质免疫印迹结果显示,肿瘤组织中IGFBP-6 mRNA表达低于相邻非肿瘤组织。基于IHC数据,263例患者中有170例IGFBP-6表达显著降低,这与肿瘤体积较大(P<0.001)、低分化腺癌(P=0.001)以及姑息性胃切除术(P=0.015)相关。此外,IGFBP-6表达降低与T3/4a/4b期疾病和淋巴结阳性转移相关(P<0.001)。Kaplan-Meier曲线显示表达降低与预后不良相关。Cox回归模型将IGFBP-6确定为独立预后因素。包含IGFBP-6表达的模型的预后价值(AIC,924.881;c指数,0.878)优于不包含IGFBP-6表达的模型(AIC,947.164;c指数,0.825)。总之,IGFBP-6参与胃腺癌的发生发展,其表达降低预示临床结局不良。