食管鳞癌中CAV-1基因的表达及甲基化状态

doi:10.3969/j.issn.1007-3969.2014.10.013

中国癌症杂志 ›› 2014, Vol. 24 ›› Issue (10): 789-793.doi: 10.3969/j.issn.1007-3969.2014.10.013

食管鳞癌中CAV-1基因的表达及甲基化状态

周珍¹,郭艳丽¹,韩立杰^1,2,郭炜¹,李书梅³,沈素朋¹,董稚明¹

1.河北医科大学第四医院肿瘤研究所病理研究室，河北石家庄 050011；
2.河北省沧州市中心医院放疗科，河北沧州 061001；
3.河北医科大学第四医院病案室，河北石家庄 050011

出版日期:2014-10-30 发布日期:2014-11-12
通信作者: 董稚明　E-mail:dongzhiming2000@163.com
基金资助:
河北省医学研究重大专项基金资助(NO: 冀财预复［2012］2056号)

Expression and methylation status of CAV-1 gene in esophageal squamous cell carcinoma

ZHOU Zhen¹, GUO Yan-li¹, HAN Li-jie^1,2, GUO Wei¹, LI Shu-mei³, SHEN Su-peng¹, DONG Zhi-ming¹

1.Laboratory of Pathology, Hebei Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang Hebei 050011, China; 2. Department of Radiotherapy, Cangzhou Central Hospital, Cangzhou Hebei 061001, China; 3. Department of Medical Records, Fourth Hospital of Hebei Medical University, Shijiazhuang Hebei 050011, China

Published:2014-10-30 Online:2014-11-12
Contact: DONG Zhi-ming E-mail: dongzhiming2000@163.com

摘要/Abstract

摘要：

背景与目的：作为重要的表观遗传学现象之一，DNA甲基化对基因表达发挥着重要的调控功能。研究表明肿瘤细胞基因组正常DNA甲基化模式异常改变所导致的肿瘤相关基因功能异常可能参与肿瘤发生与发展。本研究通过检测食管鳞状细胞癌(esophageal squamous cell carcinomas，ESCC)组织中质膜微囊蛋白-1(caveolin-1，CAV-1)基因的表达及甲基化状态，探讨CAV-1基因在食管鳞癌发生及发展中的作用。方法：分别应用甲基化特异性PCR(MSP)、RT-PCR法、免疫组织化学SP法检测食管癌及相应癌旁正常黏膜组织标本中CAV-1基因甲基化状态、mRNA及蛋白表达情况。结果：CAV-1 mRNA在食管癌和癌旁正常组织中的表达量分别为0.86±0.56和0.40±0.36，食管癌组织中CAV-1 mRNA表达量明显高于癌旁正常组织，2者差异有统计学意义(P<0.05)。CAV-1 mRNA表达与患者的淋巴结转移及肿瘤组织学分级有关(P<0.05)；食管鳞癌组织中，CAV-1蛋白表达阳性率为66.7%(34/51)；显著高于正常食管黏膜组织(15.7%，8/51)(P<0.01)。CAV-1蛋白表达与患者的淋巴结转移有关(P<0.05)，而与肿瘤的临床分期和分化程度无关(P>0.05)。51例食管癌组织中1例发生了基因启动子区甲基化，甲基化率为2.0%(1/51)；而相应癌旁正常黏膜组织中未发现有该基因的甲基化现象。食管癌组织中该基因的甲基化率与相应癌旁正常组织相比，差异无统计学意义(P>0.05)。结论：CAV-1基因在食管鳞癌组织中mRNA及蛋白表达均明显高于癌旁正常黏膜组织，该基因的高表达对于肿瘤的发生及淋巴结的转移起到了一定的促进作用；癌及癌旁组织中该基因的表达异常均与该基因的甲基化状态无关。

关键词: 食管磷癌, 甲基化, CAV-1基因, 表达

Abstract:

Background and purpose: As one of the important epigenetic phenomena, DNA methylation plays an important regulatory function for the expression of genes. Study shows that abnormal changes of DNA methylation patterns of normal tumor cell genome leads to dysfunction of cancer related gene, and this may be associated with tumor occurrence and development. The study investigated the promoter methylation and expression of caveolin-1 (CAV-1) gene in esophageal squamous cell carcinoma (ESCC), and to elucidate its role in ESCC. Methods: We used MSP approach, RT-PCR, and immunohistochemistry method respectively to examine the methylation status of the 5’CpG island of CAV-1 gene and its expression at mRNA and protein levels in tumors and corresponding normal tissues. Results: CAV-1 mRNA expression in tumor tissues (0.86±0.56) was significantly higher than that in corresponding normal tissues (0.40±0.36, P<0.05). The mRNA expression of CAV-1 was correlated with status of lymphatic metastasis and TNM stage of ESCC patients (P<0.05). The protein expression of CAV-1 in tumor specimens (66.7%, 34/51) was significantly higher than that in corresponding normal tissues (15.7%, 8/51, P<0.01). The protein expression of CAV-1 was significantly associated with lymphatic metastasis of ESCC (P<0.05), however, it was not associated with differentiation and TNM stage (P>0.05). The promoter methylation frequency of CAV-1 in tumor specimens was 2.0% (1/51), and the methylation phenomenon has not been found in corresponding normal tissues. The promoter methylation frequency of CAV-1 in tumor specimens showed no significant difference compared with the corresponding normal tissues (P>0.05). Conclusion: The mRNA and protein expression of CAV-1 in tumor specimens was significantly higher than that in corresponding normal tissues. Aberrant high expression of CAV-1 has played a certain role in promoting tumorigenesis and lymph node metastasis. The expression both in ESCC and corresponding normal tissues has no correlation with the promoter methylation status.

Key words: Esophageal squamous cell carcinoma, Methylation, CAV-1 gene, Expression

周珍,郭艳丽,韩立杰,郭炜,李书梅,沈素朋,董稚明. 食管鳞癌中CAV-1基因的表达及甲基化状态[J]. 中国癌症杂志, 2014, 24(10): 789-793.

ZHOU Zhen1, GUO Yan-li, HAN Li-jie, GUO Wei, LI Shu-mei, SHEN Su-peng, DONG Zhi-ming. Expression and methylation status of CAV-1 gene in esophageal squamous cell carcinoma[J]. China Oncology, 2014, 24(10): 789-793.

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食管鳞癌中CAV-1基因的表达及甲基化状态

Expression and methylation status of CAV-1 gene in esophageal squamous cell carcinoma

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