Ding Chenbo, Luo Junmin, Yu Weina, Gao Shaoying, Yang Liwen, Chen Chao, Feng Jihong
Department of Immunology, Zunyi Medical College, Immunology Innovation Base of Postgraduate Education in Guizhou Province Zunyi, China.
Department of Oncology, Affiliated Hospital of Zunyi Medical College Zunyi, China.
Int J Clin Exp Pathol. 2015 Mar 1;8(3):2779-86. eCollection 2015.
Gab2 (Grb2-associated binder 2), a member of the DOS/Gab family of scaffolding adapters, serves as a critical signal amplifier downstream of various growth factor receptors. Recent studies have identified that Gab2 is overexpressed in several cancer types and that increased Gab2 expression promotes cell proliferation, cell transformation, and tumor progression. Here, we show for the first time that Gab2 protein is overexpressed in clinical colorectal cancer (CRC) specimens. Elevated mRNA (P=0.014) expression and protein (P=0.003) expression of Gab2 were found in most CRC tissues compared with the matched adjacent non-tumor tissues using real-time quantitative reverse transcription PCR (qRT-PCR) and western blotting, respectively. Immunohistochemical analyses showed that Gab2 protein was upregulated in CRC tissues relative to adjacent normal tissues (P<0.001), and this overexpression was significantly correlated with lymph node metastasis (P=0.007), distant metastasis (P<0.001) and TNM stage (P=0.002). According to Kaplan-Meier model, CRC patients with Gab2-positive had a significantly poorer prognosis compared to those with Gab2-negative (P=0.007). Multivariate analysis suggested that the positive expression of Gab2 protein was an independent prognostic factor for CRC patients. In conclusion, our data demonstrated that Gab2 expression may play an important role in the progression of CRC, and underscored that Gab2 has the potential value as a prognostic predictor for CRC patients.
Gab2(Grb2相关结合蛋白2)是DOS/Gab支架衔接蛋白家族的成员,在多种生长因子受体下游充当关键的信号放大器。最近的研究发现,Gab2在几种癌症类型中过度表达,并且Gab2表达的增加会促进细胞增殖、细胞转化和肿瘤进展。在此,我们首次表明Gab2蛋白在临床结直肠癌(CRC)标本中过度表达。分别使用实时定量逆转录PCR(qRT-PCR)和蛋白质印迹法发现,与匹配的相邻非肿瘤组织相比,大多数CRC组织中Gab2的mRNA表达(P=0.014)和蛋白质表达(P=0.003)升高。免疫组织化学分析表明,相对于相邻正常组织,CRC组织中Gab2蛋白上调(P<0.001),并且这种过表达与淋巴结转移(P=0.007)、远处转移(P<0.001)和TNM分期(P=0.002)显著相关。根据Kaplan-Meier模型,Gab2阳性的CRC患者与Gab2阴性的患者相比,预后明显更差(P=0.007)。多变量分析表明,Gab2蛋白的阳性表达是CRC患者的独立预后因素。总之,我们的数据表明Gab2表达可能在CRC进展中起重要作用,并强调Gab2作为CRC患者预后预测指标具有潜在价值。