Xu Bihong, Huang Chunyu, Yang Xianzi, Li Xiangzhao, Li Liang, Ding Yanqing
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Department of Endoscopy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.
Oncol Lett. 2018 Apr;15(4):5185-5192. doi: 10.3892/ol.2018.7992. Epub 2018 Feb 7.
Human epidermal growth factor receptor 2 (HER-2) has an important clinical role in various cancers. However, the prognostic impact of HER-2 in gastric cancer (GC) is controversial. RAB1A is an important small molecule in the mechanistic target of rapamycin signalling pathway, which is one of the downstream signalling pathways of the epidermal growth factor receptor family. In recent years, the aberrant expression of RAB1A has been reported in a number of tumours, but its regulation in GC has not been extensively examined. Therefore, the present study investigated the expression pattern and prognostic significance of HER-2 and RAB1A in gastric adenocarcinoma (CAG). A comprehensive analysis was performed to examine the expression level of HER-2 and RAB1A in 280 cases of paired paraffin-embedded GAC tissues and an additional 120 archived GAC tissue samples. HER-2 and RAB1A protein expression was assessed by immunohistochemistry and cases with a 2+ score for HER-2 expression levels were subjected to fluorescence hybridization to determine the HER-2 amplification status. Furthermore, HER-2 and RAB1A mRNA expression was quantified by reverse transcription-quantitative polymerase chain reaction. The comparison of continuous data between two groups was performed using a paired-samples t-test. Clinical correlations were determined using Pearson's Chi-square and Fisher's exact tests. Kaplan-Meier survival curves were used to estimate overall survival (OS). Cox proportional hazards models were used to determine associations between HER-2 and RAB1A expression and outcomes. Regression analyses were performed to detect the correlation between the mRNA levels of HER-2 and RAB1A in GAC tissues. It was observed that RAB1A was significantly overexpressed in GAC tissues compared with normal tissues (P<0.001). Approximately 12.86% of the 280 GAC patients had HER-2 amplification. Additionally, RAB1A expression was significantly associated with a short OS (P<0.001) but there were no significant differences in survival between the HER-2 high-expression group and the HER-2 low-expression group. Additionally, the co-expression of HER-2 and RAB1A indicated poorer OS than the overexpression of each protein (P=0.001), and the two factors were significantly positively correlated in GAC (P=0.012). These findings may be used to further explore the molecular mechanisms and regulatory associations among signalling pathways in GC.
人表皮生长因子受体2（HER-2）在多种癌症中具有重要的临床作用。然而，HER-2在胃癌（GC）中的预后影响存在争议。RAB1A是雷帕霉素信号通路机制靶点中的一种重要小分子，该信号通路是表皮生长因子受体家族的下游信号通路之一。近年来，已有报道称RAB1A在多种肿瘤中存在异常表达，但其在GC中的调控尚未得到广泛研究。因此，本研究调查了HER-2和RAB1A在胃腺癌（GAC）中的表达模式及预后意义。对280例配对的石蜡包埋GAC组织及另外120例存档的GAC组织样本进行综合分析，以检测HER-2和RAB1A的表达水平。通过免疫组织化学评估HER-2和RAB1A蛋白表达，HER-2表达水平评分为2+的病例进行荧光杂交以确定HER-2扩增状态。此外，通过逆转录定量聚合酶链反应对HER-2和RAB1A mRNA表达进行定量。两组连续数据的比较采用配对样本t检验。使用Pearson卡方检验和Fisher精确检验确定临床相关性。采用Kaplan-Meier生存曲线评估总生存期（OS）。使用Cox比例风险模型确定HER-2和RAB1A表达与预后之间的关联。进行回归分析以检测GAC组织中HER-2和RAB1A mRNA水平之间的相关性。结果发现，与正常组织相比，RAB1A在GAC组织中显著过表达（P<0.001）。280例GAC患者中约12.86%存在HER-2扩增。此外，RAB1A表达与较短的OS显著相关（P<0.001），但HER-2高表达组和HER-2低表达组之间的生存率无显著差异。此外，HER-2和RAB1A的共表达表明OS比每种蛋白单独过表达时更差（P=0.001），且这两个因素在GAC中显著正相关（P=0.012）。这些发现可能有助于进一步探索GC信号通路中的分子机制和调控关联。
