Methylation and expression of PTPN22 in esophageal squamous cell carcinoma.
Methylation and expression of PTPN22 in esophageal squamous cell carcinoma.
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DOI：
10.18632/oncotarget.11581
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发表时间：
2016-09-27
期刊：
影响因子：
--
通讯作者：
Zhao K
中科院分区：
文献类型：
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作者：
Deng J;Zhang J;Wang Ch;Wei Q;Zhou D;Zhao K
食管鳞状细胞癌是一种遗传和表观遗传共同作用的致死性疾病。蛋白酪氨酸磷酸酶非受体22（PTPN 22）在食管鳞癌中的表观遗传学改变及其临床意义尚不清楚。分别在121和31对肿瘤和邻近正常组织（ANT）中进行PTPN 22及其表达的定量甲基化研究。此外，PTPN 22甲基化和临床病理参数之间的关联进行了评估。我们发现PTPN 22的甲基化水平在肿瘤组织中（66.3%）相对于ANT（62.1%）显著升高（p=0.005）。不吸烟ANT的甲基化水平（59.1%）显著低于吸烟ESCC组织（65.8%）（p=0.03）;类似地，无淋巴结浸润的ANT的甲基化水平（57.6%）显著低于有淋巴结浸润的肿瘤组织（67.5%）（p=0.001）。PTPN 22在ESCC中的表达低于正常组织，但差异无统计学显著性（p=0.55）。N1-3和III期患者中低表达率较高，而N 0和I-II期患者中高表达率较高。PTPN 22的低表达与较差的总体存活率相关（p=0.04）。总之，PTPN 22在ESCC中是高甲基化的。高甲基化与淋巴结浸润有关。PTPN 22表达可作为一种预后生物标志物，以识别高级别风险的患者。
Esophageal squamous cell carcinoma (ESCC) is a fatal disease contributed by both genetic and epigenetic factors. The epigenetic alteration of protein tyrosine phosphatase non-receptor type 22 (PTPN22) and its clinical significance in ESCC were still not yet clarified. A quantitative methylation study of PTPN22 and its expression were conducted in 121 and 31 paired tumor and adjacent normal tissue (ANT), respectively. Moreover, the association between PTPN22 methylation and clinicopathological parameters was evaluated. We found that the methylation level of PTPN22 was significantly elevated in tumor tissues (66.3%) relative to ANT (62.1%) (p=0.005). The methylation level of non-smoking ANT (59.1%) was significant lower than smoking ESCC tissue (65.8%) (p=0.03); similarly, the methylation levels in ANT with no lymph node invasion (57.6%) were significant lower than tumor tissues with lymph node invasion (67.5%) (p=0.001). PTPN22 expression in ESCC was lower than normal tissues, however the difference was not statistically significant (p=0.55). Lower expression was more frequently occurred in N1-3 and III stage patients, while higher expression was more likely to occur in N0 and I-II stage patients. Lower expression of PTPN22 was associated with poor overall survival (p=0.04). Taken together, PTPN22 was hypermethylationed in ESCC. Hypermethylation was associated with lymph node invasion. The PTPN22 expression may act as a prognostic biomarker to identify patients at risk of high grade.