Kong Dequan, Su Guoqiang, Zha Lang, Zhang Hongyu, Xiang Jifeng, Xu Wei, Tang Yucheng, Wang Ziwei
Department of Gastrointestinal Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Med Oncol. 2014 Aug;31(8):130. doi: 10.1007/s12032-014-0130-5. Epub 2014 Jul 19.
High mobility group protein A2 (HMGA2) and octamer-binding transcription factor 4 (Oct4) are transcription factors that play major roles in the acquisition of cancer stemness phenotypes and tumorigenicity of malignant neoplasms. The aim of this study was to analyze the association between HMGA2 and Oct4 expression and various clinicopathologic features in gastric cancer patients including invasion, metastasis, and clinical prognosis, in addition to overall survival. Immunohistochemistry was performed to explore the expression of HMGA2 and Oct4 in 158 gastric cancer and surrounding non-tumor tissues. Moreover, HMGA2 and Oct4 mRNA and protein levels were also detected by qRT-PCR and Western blotting, respectively, in 86 clinical tissue specimens and various gastric epithelial cell lines (GES-1, SGC7901, MKN45, and MKN27). Finally, associations between HMGA2 and Oct4 expression and clinicopathological features were analyzed by Pearson correlation coefficient. Survival analysis was performed by univariate and multivariate analyses. Taken together, we found that HMGA2 and Oct4 expression was significantly higher in gastric cancer tissues compared with non-cancerous tissues (P < 0.01), and HMGA2 and Oct4 protein levels were significantly higher in poorly differentiated gastric cancer cell lines (MKN45), moderately differentiated cell lines (SGC7901), and well-differentiated cell lines (MKN28) compared with human immortalized gastric epithelial cell lines (GES-1) (P < 0.01). Elevated HMGA2 and Oct4 levels were significantly associated with poor clinical prognosis (P < 0.05). Further conclusion showed that coexpression of HMGA2 and Oct4 in gastric cancer correlated with tumor invasion, metastasis, and clinical prognosis and predicted an unfavorable clinical outcome. These transcription factors may represent useful biomarkers to identify patients at high risk of postoperative recurrence.
高迁移率族蛋白A2（HMGA2）和八聚体结合转录因子4（Oct4）是转录因子，在恶性肿瘤的癌症干性表型获得和致瘤性中起主要作用。本研究的目的是分析HMGA2和Oct4表达与胃癌患者各种临床病理特征（包括侵袭、转移和临床预后）以及总生存期之间的关联。采用免疫组织化学法探讨158例胃癌及癌旁非肿瘤组织中HMGA2和Oct4的表达。此外，还分别通过qRT-PCR和蛋白质印迹法检测了86例临床组织标本和各种胃上皮细胞系（GES-1、SGC7901、MKN45和MKN27）中HMGA2和Oct4的mRNA和蛋白质水平。最后，通过Pearson相关系数分析HMGA2和Oct4表达与临床病理特征之间的关联。通过单因素和多因素分析进行生存分析。综合来看，我们发现胃癌组织中HMGA2和Oct4的表达明显高于非癌组织（P<0.01），与人类永生化胃上皮细胞系（GES-1）相比，低分化胃癌细胞系（MKN45）、中分化细胞系（SGC7901）和高分化细胞系（MKN28）中HMGA2和Oct4的蛋白质水平明显更高（P<0.01）。HMGA2和Oct4水平升高与不良临床预后显著相关（P<0.05）。进一步的结论表明，胃癌中HMGA2和Oct4的共表达与肿瘤侵袭、转移和临床预后相关，并预示着不良的临床结局。这些转录因子可能是识别术后复发高危患者的有用生物标志物。
