LINE-1甲基化水平与食管鳞状细胞癌免疫状态的关系

Relationship between LINE-1 methylation level and immune status in esophageal squamous cell carcinoma

目的探讨食管鳞状细胞癌(ESCC)组织中长散布核元件-1(LINE-1)甲基化水平与免疫状态之间的关系。方法收集107例经术后病理证实为ESCC的肿瘤组织样本,采用亚硫酸氢盐焦磷酸测序法检测ESCC组织中LINE-1甲基化水平。根据HE染色法和免疫组织化学染色法检测4种组织学淋巴细胞反应[克罗恩样淋巴样反应、瘤周淋巴细胞反应、间质淋巴细胞反应、肿瘤浸润淋巴细胞(TILs)反应],并进一步分析ESCC组织中LINE-1甲基化水平与组织学淋巴细胞反应及患者临床病理特征的关系。结果ESCC组织中LINE-1平均甲基化率为(64.27±9.72)%,中位值为63.51%(43.81%~85.10%)。ESCC组织中LINE-1甲基化水平与患者年龄、淋巴结转移、TNM分期、瘤周淋巴细胞反应有关(P<0.05)。缺失/低瘤周淋巴细胞反应的肿瘤组织中LINE-1基因甲基化率低于中、高瘤周淋巴细胞反应的肿瘤组织(P<0.05)。经单因素和多因素Logistic回归模型分析,ESCC组织中LINE-1低甲基化水平是缺失/低瘤周淋巴细胞反应的独立危险因素(P trend<0.001)。结论ESCC组织中LINE-1甲基化水平与患者临床病理、分子特征有关,此外LINE-1低甲基化水平是ESCC组织中缺失/低瘤周淋巴细胞反应的独立危险因素。

Objective To investigate the relationship between methylation level of long-interspersed nucleotide element-1(LINE-1)and immune status in esophageal squamous cell carcinoma(ESCC).Methods LINE-1 methylation levels in ESCC were detected by bisulfite pyrosequencing in 107 tumor tissue samples with ESCC which were confirmed by postoperative pathology.Four kinds of histological lymphocyte reactions[Crohn s-like lymphoid reaction,peritumoral lymphocyte reaction,interstitial lymphocyte reaction,tumor infiltrating lymphocytes(TILs)reaction]were detected by HE staining and immunohistochemical staining,and the relationship between the LINE-1 methylation level in ESCC and the histological lymphocyte reaction and the clinicopathological characteristics of patients was further analyzed.Results The average methylation rate of LINE-1 in ESCC was(64.27±9.72)%,and the median was 63.51%(43.81%~85.10%).The level of LINE-1 methylation in ESCC was correlated with age,lymph node metastasis,TNM stage and peritumoral lymphocyte reaction(P<0.05).The methylation rate of LINE-1 gene in tumors with absent/low peritumoral lymphocyte reaction was lower than that in tumors with intermediate or high peritumoral lymphocyte reaction(P<0.05).Univariate and multivariate Logistic regression analysis showed that LINE-1 hypomethylation in ESCC was an independent risk factor for absent/low peritumoral lymphocyte reaction(P trend<0.001).Conclusion The level of LINE-1 methylation in ESCC is related to the clinicopathological and molecular features of patients.In addition,LINE-1 hypomethylation is an independent risk factor for ESCC absent/low peritumoral lymphocyte reaction in ESCC.