中国癌症杂志 ›› 2015, Vol. 25 ›› Issue (6): 416-423.doi: 10.3969/j.issn.1007-3969.2015.06.003

• 论著 • 上一篇    下一篇

干细胞转录因子SOX2、OCT4在不同分化程度胃癌组织中的表达及其临床意义

徐毅,丁伟基,李文鹏,陈跃达,魏斌,谢永进,罗琪,黄正接   

  1. 福建医科大学第一临床医学院,厦门大学附属第一医院厦门市肿瘤中心胃肠外科,
    福建 厦门 361003
  • 出版日期:2015-06-30 发布日期:2015-08-14
  • 通信作者: 黄正接 E-mail:h74zj@126.com
  • 基金资助:
    福建省医学创新课题(2012-CXB-29);福建省科技计划重点项目(2014D017);厦门市科技计划项目(3502Z20134011、3502Z20124018)。

The expression and clinical significance of stem cell transcription factor SOX2, OCT4 in gastric cancer tissues varying degrees of cell differentiation

XU Yi, DING Weiji, LI Wenpeng, CHEN Yueda, WEI Bin, XIE Yongjin, LUO Qi, HUANG Zhengjie   

  1. The First Clinical Medical College, Fujian Medical University; Department of Gastrointestinal Surgery, the First Affiliated Hospital of Xiamen University, Xiamen Cancer Center, Xiamen Fujian 361003, China
  • Published:2015-06-30 Online:2015-08-14
  • Contact: HUANG Zhengjie E-mail: h74zj@126.com

摘要:         背景与目的:肿瘤组织的分化程度是决定胃癌预后的重要因素,本研究检测胃癌组织中性别决定相关基因簇2(sex determining region Y-box 2,SOX2)、八聚体结合蛋白-4(octamer binding factor 4,OCT4)的表达,探讨SOX2、OCT4的表达与胃癌患者临床病理因素及预后的关系及意义。方法:通过实时定量PCR(quantitative real-time PCR,qRT-PCR)、蛋白[质]印迹法(Western blot)和免疫组化检测了60例分化程度不同的胃癌组织与正常黏膜组织中SOX2和OCT4的mRNA及蛋白的表达量,并分析SOX2OCT4基因的表达水平与患者临床病理参数的关系。结果:qRT-PCR、Western blot检测显示,高分化胃癌组织SOX2 mRNA和蛋白的相对表达量与正常胃黏膜组织比较差异无统计学意义(t=0.103 3,P>0.05;t=0.116,P>0.05),但显著高于中分化胃癌组织(t=12.48,P<0.05;t=22.78,P<0.05)和低分化胃癌组织(t=17.56,P<0.05;t=30.00,P<0.05),差异有统计学意义。与SOX2相反,高分化胃癌组织OCT4 mRNA的相对表达量与正常胃黏膜组织比较差异无统计学意义(t=2.436,P>0.05;t=1.064,P>0.05),但显著低于中分化胃癌组织(t=13.23,P<0.05;t=25.56,P<0.05)和低分化胃癌组织(t=12.10,P<0.05;t=69.48,P<0.05),差异有统计学意义。免疫组化显示,高分化胃癌组织中SOX2的阳性表达率(10/21)高于中分化胃癌组织(7/20)和低分化胃癌组织(2/19,P<0.05),高分化胃癌组织中OCT4的阳性表达率(2/21)低于中分化胃癌组织(6/20)和低分化胃癌组织(12/19,P<0.05),与临床病理参数相比较,胃癌中SOX2和OCT4蛋白的表达与患者的性别、年龄无关,差异无统计学意义(P>0.05)。与病理分期、浸润程度、淋巴结转移相关(P<0.05)。结论:SOX2基因的低表达水平和OCT4的高表达水平促进胃癌的发生、发展和侵袭,有望成为胃癌诊断、治疗和预后判断的一个指标。

关键词: 胃肿瘤, 性别决定相关基因簇2, 八聚体结合蛋白-4, 分化程度

Abstract:         Background and purpose: Differentiation of tumor tissue is an important factor on determining the prognosis of gastric cancer. This study aimed to investigate the expression levels and clinical significance of gender determining region Y-box 2 (SOX2) gene and octamer binding factor 4 (OCT4) gene in gastric cancer tissues varying different differentiation degrees. Methods: Sixty cases with gastric cancer were recruited in this study. The gastric cancer tissues and corresponding normal mucosa of the 60 cases were obtained. The mRNA and protein level of SOX2, OCT4 gene are evaluated by the quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry, respectively. The relationship between the expression levels of SOX2, OCT4 gene and clinical pathological parameters were also analyzed in this study. Results: The expression of SOX2 in both mRNA and protein levels had no significant difference between the well-differentiated gastric cancer tissues and normal gastric mucosa (mRNA levels: t=0.1033, P>0.05; protein levels: t=0.116, P>0.05). However, both the mRNA and protein expression of SOX2 in patients with well-differentiated gastric cancer tissues were significant higher than not only in patients with moderately differentiated gastric carcinoma (mRNA levels: t=12.48, P<0.05; protein levels: t=22.78, P<0.05) but also in patients with than poorly differentiated gastric carcinoma (mRNA levels: t=17.56, P<0.05; protein levels: t=30.00, P<0.05). In contrast to SOX2, both the mRNA and protein expression of OCT4 in patients with well-differentiated gastric cancer tissues were significant lower than not only in patients with moderately differentiated gastric carcinoma (mRNA levels: t=13.23, P<0.05; protein levels: t=25.56, P<0.05) but also in patients with poorly differentiated gastric carcinoma (mRNA levels: t=12.10, P<0.05; protein levels: t=69.48, P<0.05). There was no significance of OCT4 mRNA and protein expression between the well-differentiated gastric cancer tissues and normal gastric mucosa (mRNA levels: t=2.436, P>0.05; protein levels: t=1.064, P>0.05). Immunohistochemical study demonstrated that the positive rate of SOX2 in patients with well-differentiated gastric cancer tissues (10/21) were higher than in patients with not only moderately differentiated gastric carcinoma (7/20) but also poorly differentiated gastric carcinoma (2/19, P<0.05), while the positive rate of OCT4 in cases with well-differentiated gastric cancer tissues (2/21) were lower than in cases with not only moderately differentiated gastric carcinoma (6/20) but also the poorly differentiated gastric carcinoma (12/19, P<0.05). There was no correlation between the expression of SOX2, OCT4 in gastric cancer and gender or age (P>0.05). Nevertheless, the expression of SOX2, OCT4 were positive or negative correlated with the pathological staging, the degree of infiltration and lymph node metastasis (P<0.05). Conclusion: Decreased SOX2 expression and increased expression level of OCT4 can promote the formation, development and invasion of gastric cancer and they may become biomarkers or the diagnosis, treatment and prognosis evaluation in gastric carcinoma.

Key words: Stomach neoplasms, Sex determining region Y-box 2, Octamer binding factor 4, Cell differentiation