SOCS-3基因在结肠癌中的表达及甲基化测定

Expression and methylation of SOCS-3 gene in human colon carcinoma

关键词:  SOCS-3  结肠肿瘤  甲基化

Key words:  SOCS-3

摘要:

目的通过对细胞因子信号转导抑制因子-3（suppressor of cytokine siganaling-3，SOCS-3）基因在结肠癌和癌旁组织中的表达及其启动子甲基化状态的测定，探讨其与结肠癌发生、发展和转移等的关系。方法收集40例结肠癌患者的肿瘤标本，20例癌旁组织以及10例正常结肠组织．运用甲基化特异性PCR测定SOCS-3基因CpG岛甲基化状态，同时运用实时定量PCR分析SOCS-3基因在结肠癌组织中的表达水平。结果40例结肠癌组织中有34例（85％）存在SOCS-3基因CpG岛的异常甲基化，癌旁组织中为2例（10％），而正常结肠组织中没有检测到SOCS-3基因呈CpG岛甲基化；结肠癌组织中SOCS-3基因CpG岛甲基化组与无甲基化组相比．其SOCS-3基因的相对表达量明显减少（P〈0．05），表明SOCS-3基因CpG岛甲基化可导致SOCS-3基因表达降低。与患者临床资料结合分析，发现SOCS-3基因CpG岛甲基化与性别、年龄无关（P〉0．05），而与肿瘤病理分级和TNM分期有关（P〈0．05）。结论结肠癌中存在SOCS-3基因CpG岛异常甲基化，且因CpG岛的甲基化导致其基因表达降低。SOCS-3基因CpG岛甲基化可能参与了结肠癌的发生、发展和转移。

Abstract:

Objective To study the relationship of suppressor of cytokine signaling-3 （SOCS-3） gene with genesis, progress and metastasis of colon cancer by detecting the expression and methylation of its promoter in human colon carcinoma. Methods Methylation of CpG island in SOCS-3 gene were examined in 40 human colon carcinoma specimens, 20 periphtumoral tissue specimens and 10 corresponding normal colon tissue specimens by methylation-specific polymerase chain reaction. The real-time PCR was applied to check the corresponding SOCS-3 expression. Results Aberrant methylation of SOCS-3 CpG island was detected in 34 of 40 （85%） colon carcinoma, in 2 of 20 （10%） periphtumoral tissue, while no SOCS-3 CpG island methylation was found in the normal colon tissue specimens. Aberrant methylation of the SOCS-3 CpG island greatly inhibited the gene expression in colon carcinoma in comparison of the colon carcinoma specimens with no SOCS-3 CpG island methylation （P〈0.05）. Correlation was found between SOCS-3 aberrant methylation and the clinic pathological feature as tumor pathological rating and TNM staging. Conclusion Aberrant methylation of SOCS-3 CpG island exists in human colon carcinoma, which inhibits SOCS-3 gene expression. SOCS-3 may be associated with the initiation, development and metastasis of colon carcinoma.