Epigenetic inactivation of SOCS-1 by CpG island hypermethylation in human gastric carcinoma
Epigenetic inactivation of SOCS-1 by CpG island hypermethylation in human gastric carcinoma
复制标题
DOI：
10.1002/ijc.20521
复制
发表时间：
2004-12-20
影响因子：
6.4
通讯作者：
Yasui, W
中科院分区：
文献类型：
--
作者：
Oshimo, Y;Kuraoka, K;Yasui, W
细胞因子信号转导抑制因子（SOCS）-1通过几种细胞因子抑制Janus激酶（JAK）/信号转导和转录激活因子（STAT）途径的信号转导，并具有肿瘤抑制活性。SOCS-1 CpG岛的甲基化已显示在某些人类癌症中使SOCS-1基因失活。在我们的研究中，我们调查了SOCS-1基因甲基化状态的甲基化特异性PCR在75胃癌（GC）组织，25相应的非肿瘤性粘膜和10个正常胃粘膜从健康的年轻人。我们还进行了亚硫酸氢盐测序的DNA从2 GC组织。另外，用定量RTPCR检测50例胃癌中SOCS-1 mRNA的表达。在75例胃癌组织中的33例（44%）和25例相应的非肿瘤性粘膜中的3例（12%）中检测到SOCS-1基因的超甲基化;发生率有显著差异（p = 0.004）。10例健康人正常胃组织均未出现甲基化。SOCS-1基因甲基化与淋巴结转移、晚期肿瘤分期和胃癌组织中SOCS-1表达降低相关（分别为p = 0.009、0.034和0.002）。胃癌组织中SOCS-1的表达减少与淋巴结转移和晚期肿瘤分期相关（分别为p = 0.013和0.002）。我们的研究结果表明，转录失活的SOCS-1基因的甲基化可能参与了胃癌的发展，进展和转移。(C)2004 Wiley-Liss，Inc.
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. In our study, we investigated methylation status of the SOCS-1 gene by methylation-specific PCR in 75 gastric carcinoma (GC) tissues, 25 corresponding nonneoplastic mucosae and 10 normal gastric mucosae from healthy young individuals. We also performed bisulfite sequencing of DNAs from 2 GC tissues. In addition, SOCS-1 mRNA levels were examined in 50 GCs by quantitative RTPCR. Hypermethylation of the SOCS-1 gene was detected in 33 (44%) of 75 GC tissues and in 3 (12%) of 25 corresponding nonneoplastic mucosae; the incidence was significantly different (p = 0.004). None of the 10 normal gastric tissues from healthy individuals showed hypermethylation. Methylation of the SOCS-I gene was associated with lymph node metastasis, advanced tumor stage and reduced expression of SOCS-1 in GC tissues (p = 0.009, 0.034 and 0.002, respectively). Reduced expression of SOCS-1 in GC tissues was associated with lymph node metastasis and advanced tumor stage (p = 0.013 and 0.002, respectively). Our results suggest that transcriptional inactivation of the SOCS-1 gene by hypermethylation may be involved in development, progression and metastasis of GC. (C) 2004 Wiley-Liss, Inc.