摘要
目的:探讨SOCS-1基因在胃癌和癌旁组织中的表达及其启动子甲基化状态与胃癌发生、发展和转移等的关系。方法:采集45例胃癌病人的肿瘤标本、18例癌旁胃粘膜组织以及10例正常胃粘膜组织,运用甲基化特异性PCR反应研究胃癌组织中SOCS-1基因CpG岛甲基化状态,同时运用实时定量PCR分析SOCS-1基因的表达。结果:45例胃癌标本中有21例(46.7%)SOCS-1基因呈CpG岛甲基化,癌旁组织中为2例(11.1%),而10例正常胃粘膜组织中则未发现SOCS-1基因CpG岛甲基化;SOCS-1基因CpG岛甲基化组的SOCS-1基因表达量与无SOCS-1基因CpG岛甲基化组相比,其基因相对表达量明显减少(P<0.05),表明SOCS-1基因CpG岛甲基化可抑制SOCS-1基因表达。与病人临床病理特征相结合比较,发现SOCS-1基因CpG岛甲基化与年龄、性别无关,与肿瘤分化程度及TNM分期等因素有关。结论:在胃癌中存在SOCS-1基因CpG岛甲基化,且由于CpG岛甲基化而促使基因表达抑制。SOCS-1基因CpG岛甲基化在胃癌的发生、发展中可能具有一定的意义。
Objective:Suppressor of cytokine signaling(SOCS)-1 inhibits signaling of the Janus kinase(JAK)/signal transducers and activators of transcription(STAT) pathway by several cytokines and has tumor suppressor activity.Methylation of the SOCS-1 CpG island has been shown to inactivate the SOCS-1 gene in certain human cancers.Methods:To investigate methylation status of the SOCS-1 gene by methylation-specific PCR in 45 gastric carcinoma(GC) tissues,18 corresponding nonneoplastic mucosae and 10 normal gastric mucosae from healthy young individuals.In addition,SOCS-1 mRNA levels were examined in 30 GCs by quantitative RT-PCR.Results:Hypermethylation of the SOCS-1 gene was detected in 21(46.7%) of 45 GC tissues and in 2(11.1%) of 18 corresponding nonneoplastic mucosae;the incidence was significantly different(P= 0.0081).None of the 10 normal gastric tissues from healthy individuals showed hypermethylation.Methylation of the SOCS-1 gene was associated with lymph node metastasis,advanced tumor stage and reduced expression of SOCS-1 in GC tissues(P= 0.003 2,0.004 0 and 0.002 6,respectively).Reduced expression of SOCS-1 in GC tissues was associated with lymph node metastasis and advanced tumor stage(P=0.014 3 and 0.002 5,respectively).Conclusion: transcriptional inactivation of the SOCS-1 gene by hypermethylation may be involved in development,progression and metastasis of GC.
基金
湖北省教育厅资助项目(编号:T200808)
