Tumor Long-interspersed Nucleotide Element-1 Methylation Level and Immune Response to Esophageal Cancer
Tumor Long-interspersed Nucleotide Element-1 Methylation Level and Immune Response to Esophageal Cancer
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DOI：
10.1097/sla.0000000000003264
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发表时间：
2020-12-01
影响因子：
9
通讯作者：
Baba, Hideo
中科院分区：
文献类型：
--
作者：
Kosumi, Keisuke;Baba, Yoshifumi;Baba, Hideo
目的：探讨肿瘤长分布核苷酸元件-1(LINE-1)甲基化水平与食管癌免疫应答的关系。背景：有证据表明，免疫细胞的丰度与食道癌患者的良好预后之间存在相关性。越来越多的证据表明，肿瘤LINE-1低甲基化在食道癌的侵袭行为中起关键作用，进而导致不良预后。方法：利用292例食管癌的无偏数据库，采用焦磷酸测序方法检测肿瘤LINE-1甲基化水平，并检测食管癌组织中T细胞密度(CD8和FOXP3)和淋巴细胞反应类型(滤泡淋巴细胞反应、瘤周淋巴细胞反应、间质淋巴细胞反应和肿瘤浸润性淋巴细胞)与肿瘤LINE-1甲基化的关系。结果：Line-1低甲基化与男性和晚期癌症相关(P=0.03和P=0.048)。肿瘤LINE-1甲基化水平与瘤周淋巴细胞反应呈显著正相关(P=0.004)，与其他指标无相关性。与LINE-1高甲基化组相比，LINE-1低甲基化组瘤周淋巴细胞反应明显降低(单变量优势比0.32，95%可信区间0.16~0.64，P=0.002)。在控制包括疾病分期在内的潜在混杂因素的多变量模型中，也观察到了类似的结果(多变量优势比0.31，95%可信区间0.14~0.66，P=0.004)。结论：肿瘤LINE-1低甲基化水平与瘤周淋巴细胞反应减弱有关，为进一步研究TLE-1低甲基化与宿主免疫在食道癌发生中的潜在交互作用提供了动力。
Objective: To examine the relationship between tumor long-interspersed nucleotide element-1 (LINE-1) methylation level and immune response to esophageal cancer. Background: Evidence points to a correlation between the abundance of immune cells and a favorable prognosis in esophageal cancer patients. Accumulating evidence indicates a critical role of tumor LINE-1 hypomethylation in the aggressive behavior of esophageal cancer, which in turn leads to an unfavorable prognosis. Methods: Utilizing a nonbiased database of 292 resected esophageal cancers, we measured tumor LINE-1 methylation level by pyrosequencing assay, and examined the relationship between LINE-1 methylation and the density of T cells (CD8 and FOXP3) and the lymphocytic reaction patterns (follicle lymphocytic reaction, peritumoral lymphocytic reaction, stromal lymphocytic reaction, and tumor-infiltrating lymphocytes) in esophageal carcinoma tissue. Results: LINE-1 hypomethylation was associated with male gender and advanced stage cancer (P = 0.03 and P = 0.048, respectively). Tumor LINE-1 methylation level was significantly positively associated with peritumoral lymphocytic reaction (P = 0.004), but not with others. Compared with LINE-1 hypermethylation group, LINE-1 hypomethylation group showed much lower level of peritumoral lymphocytic reaction (univariable odds ratio 0.32, 95% confidence interval 0.16-0.64, P = 0.002). In multivariable model to control for potential confounders including disease stage, the similar finding was observed (multivariable odds ratio 0.31, 95% confidence interval 0.14-0.66, P = 0.004). Conclusions: Tumor LINE-1 hypomethylation level is associated with a diminished peritumoral lymphocytic reaction, providing impetus for further investigations on potential interactive roles of tumor LINE-1 hypomethylation and host immunity in esophageal cancer development.