贲门腺癌中分泌型卷曲相关蛋白4、5基因启动子区甲基化状态研究

doi:10.3969/j.issn.1004-616x.2010.01.004

癌变·畸变·突变 ›› 2010, Vol. 22 ›› Issue (1): 14-0018.doi: 10.3969/j.issn.1004-616x.2010.01.004

贲门腺癌中分泌型卷曲相关蛋白4、5基因启动子区甲基化状态研究

王馥丽1;靳国梁2;郭　炜3;郭艳丽3;董稚明3

1. 唐山市开滦医院病理科，唐山 063000； 2. 河北省磁县肿瘤医院病理科，磁县 056500; 3. 河北医科大学第四医院肿瘤研究所病理研究室，石家庄 050011

收稿日期:2009-06-30 修回日期:2009-09-17 出版日期:2010-01-30 发布日期:2010-01-30
通讯作者: 董稚明

Aberrant promoter methylation of SFRP4 and SFRP5 gene in gastric cardia adenocarcinoma

WANG Fu-li1;JIN Guo-liang2;GUO Wei3;GUO Yan-li3; DONG Zhi-ming3

1. Department of Pathology, Kailuan Hospital of Tangshan, Tangshan 063000; 2. Department of Pathology , Cixian Cancer Hospital,Cixian 056500; 3. Department of Pathology ,The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011,

Received:2009-06-30 Revised:2009-09-17 Online:2010-01-30 Published:2010-01-30
Contact: DONG Zhi-ming

摘要/Abstract

摘要： 目的：研究贲门腺癌(gastric cardia adenocarcinoma，GCA)中分泌型卷曲相关蛋白4(secreted frizzled related protein 4, SFRP4)及SFRP5基因启动子区甲基化状态与贲门腺癌发生发展的关系。方法：采用甲基化特异性PCR(methylation specific PCR，MSP)方法检测94例GCA组织及47例相应癌旁正常组织中SFRP4和SFRP5基因的甲基化情况，并分析其与临床病理特征之间的关系。结果： 94例GCA组织中SFRP4 基因甲基化率为68.1％(64/94)，显著高于癌旁正常组织中的甲基化发生率8.5％(4/47)(P<0.01)；SFRP5基因在贲门腺癌组织中的甲基化发生率为79.8％(75/94)，显著高于癌旁正常组织中的甲基化发生率12.8％(16/47)(P<0.01)。SFRP4基因在高、中分化腺癌组甲基化发生率为35％(14/40)，显著低于低分化腺癌组的发生率92.6％(50/54)(P<0.01)；SFRP4基因在无淋巴结转移组的甲基化发生率为60.5％(23/38)，低于有淋巴结转移组73.2％(41/56)，但其差异无统计学意义(P>0.05)。SFRP5基因在低分化腺癌组甲基化发生率为85.1％(46/54)，高于高、中分化腺癌组甲基化发生率72.5％(29/ 40)，但其差异无统计学意义(P>0.05)；SFRP5基因甲基化发生率在无淋巴结转移组为65.8％(25/38)，显著低于有淋巴结转移组89.3％(50/56)(P<0.05)。57例贲门腺癌组织中SFRP4和SFRP5基因同时发生甲基化者，高、中分化18例，低分化39例，两者间的差异具有统计学意义(P<0.05)。结论： SFRP4和SFRP5基因可能参与了贲门腺癌的发生，SFRP4, SFRP5基因的高甲基化状态与贲门腺癌的恶性行为有关。

关键词: 贲门腺癌, 甲基化, 分泌型卷曲相关蛋白4, 分泌型卷曲相关蛋白5

Abstract: OBJECTIVE: We investigated the promoter methylation of secreted frizzled-related protein 4(SFRP4) and SFRP5 gene in gastric cardia adenocarcinoma (GCA). METHODS: Methylation specific PCR (MSP) method was used to examine the methylation status of the 5' CpG island of SFRP4 and SFRP5 genes in 94 tumors and 47 corresponding normal tissues. RESULTS: Methylation frequencies of SFRP4 and SFRP5 genes in tumors were 68.1％(64/94)and 79.8％(75/94), respectively, significantly higher than that in corresponding normal tissues (8.5％ and 12.8％, respectively)(P<0.01). Methylation frequencies of SFRP4 in poor differentiation group (92.6％,50/54)was significantly higher than that in moderate and poor-moderate differentiation groups (35％,14/40). Methylation frequencies of SFRP5 in lymph node metastasis group (89.3％,50/56) was significantly higher than that in no lymph node metastasis group (65.8％,25/38). Methylation frequencies of SFRP5 in poor differentiation group was higher than that in moderate and poor-moderate differentiation groups, and SFRP4 in lymph node metastasis group was higher than that in no lymph node metastasis group but without significant difference(P>0.05). 57 cases of GCA showed simultaneous methylation of SFRP4 and SFRP5 genes, including 18 moderate and poor-moderate differentiation tumors, and 39 moderate differentiation tumors. Simultaneous methylation frequencies of SFRP4 and SFRP5 genes in moderate andpoor-moderate differentiation groups was significantly lower than that in moderate group. CONCLUSION: SFRP4 and SFRP5 genes might be associated with oncogenanesis of GCA and hypermethylation of these genes might be related to the malignant behavior of GCA.

Key words: gastric cardia adenocarcinoma, methylation, secreted frizzled related protein 4, secreted frizzled related protein 5

中图分类号:

R735.2

王馥丽, 靳国梁, 郭　炜, 郭艳丽, 董稚明. 贲门腺癌中分泌型卷曲相关蛋白4、5基因启动子区甲基化状态研究[J]. 癌变·畸变·突变, 2010, 22(1): 14-0018.

WANG Fu-li, JIN Guo-liang, GUO Wei, GUO Yan-li, DONG Zhi-ming. Aberrant promoter methylation of SFRP4 and SFRP5 gene in gastric cardia adenocarcinoma[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2010, 22(1): 14-0018.

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贲门腺癌中分泌型卷曲相关蛋白4、5基因启动子区甲基化状态研究

Aberrant promoter methylation of SFRP4 and SFRP5 gene in gastric cardia adenocarcinoma

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