Expression of CLIC4 in Gastric Carcinoma Tissues and Its Relevance to Microsatellite Instability
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摘要:目的
探讨微卫星DNA不稳定性在胃癌发生中的作用及其与CLIC4基因表达的关系。
方法采用PCR、非变性聚丙烯酰凝胶电泳及银染法检测40例胃癌组织及其相应的手术切缘正常组织中D1S234、D1S199、D1S507的微卫星不稳定性（MSI）；同时用免疫组织化学检测该40例及另外55例胃癌组织中CLIC4的表达。
结果D1S234、D1S199和D1S507阳性率分别为25%（10/40）、27.5%（11/40）和5%（2/40）。各组织病理类型之间差异无统计学意义（P > 0.05）。40例胃癌组织中，CLIC4在肿瘤实质阳性率为25%（10/40），肿瘤间质阳性率为67.5%（27/40），同时阳性率为15%（6/40），同时阴性率为12.5%（5/40）。Spearman等级相关分析显示D1S199与CLIC4肿瘤实质阳性率呈正相关（r=0.137, P=0.042），D1S507与CLIC4肿瘤间质阳性率呈负相关（r=-4.22, P=0.009）。95例胃癌组织中，CLIC4在肿瘤间质阳性率为72.6%（69/95），肿瘤实质阳性率为51.6%（49/95），同时阳性率为24.2%（23/95）。肿瘤间质阳性率明显高于肿瘤实质阳性率（χ2=8.945, P=0.003），肿瘤间质阳性病例主要为低分化及黏液腺癌，肿瘤实质阳性病例主要为高-中分化腺癌。随着肿瘤分化程度的降低，CLIC4间质阳性率增加。
结论D1S199与D1S507的MSI可能与胃癌的发生密切相关；CLIC4可能与胃癌的肿瘤间质成纤维化有关，促进了胃癌的演进。
Abstract:Objective To investigate the role of microsatellite instability(MSI) in gastric carcinoma and its relationship with CLIC4 expression. Methods The MSI of D1S234, D1S199, D1S507 in 40 cases of gastric carcinoma and paired normal control tissues were detected by PCR, native polyacrylamide gel electrophoresis and silver staining; and the expression of CLIC4 in these 40 cases and another 55 cases were detected by immunohistochemical analysis at the same time. Results The MSI positive rate of D1S234, D1S199 and D1S507 were 25% (10/40), 27.5% (11/40) and 5% (2/40), respectively. There was no statistically significant difference among various histological types (P > 0.05). In 40 cases of gastric carcinoma tissues, the positive rate of CLIC4 in tumor epithelial cells was 25%(10/40), and in tumor stroma was 67.5%(27/40), the negative and positive rates in both tumor epithelial cells and stroma were 15%(6/40) and 12.5%(5/40), respectively. Spearman rank correlation analysis showed that D1S199 MSI was positively correlated with CLIC4 positive rate in tumor epithelial cells (r=0.137, P=0.042), and D1S507 MSI was negatively correlated with CLIC4 positive rate in tumor stroma (r=-4.22, P=0.009). In 95 cases of gastric cancer specimens, the positive rate of CLIC4 in tumor stroma was 72.6%(69/95), in tumor epithelial cells was 51.6%(49/95), and the positive rate in both was 24.2%(23/95). The positive rate of CLIC4 in tumor stroma was significantly higher than that in tumor epithelial cells (χ2=8.945, P=0.003), tumor stroma positive cases were mainly poorly-differentiated and mucous adenocarcinoma, and tumor epithelial positive cases were mainly well-moderately differentiated adenocarcinoma. CLIC4 interstitial positive rate was increased in poorly-differentiated cases. Conclusion MSI of D1S199 and D1S507 are intimately related with the occurrence of gastric carcinoma; CLIC4 may be associated with tumor interstitial fibrosis in gastric cancer, and promote the evolution of gastric carcinoma.
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Key words:
- astric carcinoma /
- CLIC4 /
- Microsatellite instability
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致谢: 本研究部分工作在北京大学临床肿瘤学院/北京大学肿瘤医院完成，得到了季加孚教授及其团队的指导与支持，在此表示深深的感谢！
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图 1 胃癌组织中的MSI判断标准
Figure 1 Judgement standard of microsatellite instability (MSI) in gastric tissues
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图 2 CLIC4在不同胃组织中的表达(SP×100)
Figure 2 Expression of CLIC4 in different gastric tissues (SP×100)
表 2 胃癌组织中MSI及其与组织分化程度之间的关系
Table 2 MSI of gastric cancer tissue and its relationship with histological histopathologic differentiation degree
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