Department of Gastroenterology, The Drum Tower Hospital Affiliated to Medical School of Nanjing University, No. 321 Zhongshan Road, Nanjing 210008, People's Republic of China.
Dig Dis Sci. 2012 Aug;57(8):2055-62. doi: 10.1007/s10620-012-2152-1. Epub 2012 May 6.
It has been suggested that STAT3 signaling plays important roles in regulating epigenetic aberrance during tumorigenesis, especially in the expression of certain key epigenetic enzymes such as DNMTs, HDACs, and HMTs. However, there has been no report on the relationship of STAT3 signaling and epigenetic aberrance in gastrocarcinogenesis.
The purpose of this study was to explore the interrelationship of STAT3 signaling pathway and epigenetic aberrance in gastrocarcinogenesis.
Immunohistochemistry was utilized to examine the protein expressions of pSTAT3, DNMT1, HDAC1, and EZH2 in 153 tissue specimens, including 20 of normal gastric epithelium tissue, 21 of intestinal metaplasia (IM), 24 of dysplasia (DYS), 23 of early gastric cancer (EGC) and 65 of advanced gastric cancer (AGC), and then analyze their possible relationship with clinicopathological factors.
We found that the four protein expressions were obviously enhanced following the malignant process of gastric carcinogenesis. Pearson correlation analysis of all the pathological groups showed that expression of pSTAT3 was highly associated with DNMT1, but not with HADC1 and EZH2. However, significant correlations were detected among the expression of DNMT1, HDAC1, and EZH2. Further analysis of each pathological group demonstrated that pSTAT3's expression was dramatically related with DNTM1 in the IM (P = 0.021) and EGC groups (P = 0.013) and correlated with EZH2 in the DYS group (P = 0.020). Furthermore, pSTAT3's expression was associated with T staging (P = 0.015) in the AGC group, whereas DNMT1 was associated with gender (P = 0.021), HDAC1 with Lauren classification (P = 0.007), and EZH2 with T staging (P = 0.003) and lymphatic staging (P = 0.038).
The STAT3 signaling pathway may correlate with epigenetic aberrance during gastrocarcinogenesis.
有研究表明，STAT3 信号通路在肿瘤发生过程中调节表观遗传异常方面发挥着重要作用，尤其是在某些关键表观遗传酶（如 DNMTs、HDACs 和 HMTs）的表达方面。然而，目前尚无 STAT3 信号通路与胃癌发生过程中表观遗传异常之间关系的报道。
本研究旨在探讨 STAT3 信号通路与胃癌发生过程中表观遗传异常之间的相互关系。
采用免疫组织化学方法检测 153 例组织标本中 pSTAT3、DNMT1、HDAC1 和 EZH2 的蛋白表达情况，其中包括 20 例正常胃黏膜组织、21 例肠上皮化生（IM）、24 例异型增生（DYS）、23 例早期胃癌（EGC）和 65 例进展期胃癌（AGC），并分析其与临床病理因素的可能关系。
我们发现，随着胃癌癌变过程的进行，这四种蛋白的表达明显增强。对所有病理组进行 Pearson 相关性分析表明，pSTAT3 的表达与 DNMT1 高度相关，但与 HDAC1 和 EZH2 不相关。然而，DNMT1、HDAC1 和 EZH2 的表达之间存在显著相关性。对每个病理组的进一步分析表明，在 IM（P = 0.021）和 EGC 组（P = 0.013）中，pSTAT3 的表达与 DNMT1 显著相关，而在 DYS 组中与 EZH2 相关（P = 0.020）。此外，在 AGC 组中，pSTAT3 的表达与 T 分期（P = 0.015）相关，而 DNMT1 与性别（P = 0.021）相关，HDAC1 与 Lauren 分类（P = 0.007）相关，EZH2 与 T 分期（P = 0.003）和淋巴转移分期（P = 0.038）相关。
STAT3 信号通路可能与胃癌发生过程中的表观遗传异常有关。
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