YTHDF2和TET2在非小细胞肺癌中的表达及意义

Expression and Significance of YTHDF2 and TET2 in Non-Small Cell Lung Cancer

摘要: 目的：本研究旨在探讨YTH结构域连接蛋白2 (YTH binding protein 2, YTHDF2)和十十一易位酶2 (ten- eleven translocation 2, TET2)在非小细胞肺癌中的表达及意义。方法：首先，利用在线生信工具获取TET的RNA甲基化位点，并分析YTHDF2和TET2的相关性，以及预后价值。然后，用免疫组化法检测52例非小细胞肺癌和正常肺组织中YTHDF2和TET2的表达，并分析非小细胞肺癌组织中两者的表达及与临床病理特征和预后的关系。结果：TET2上存在大量N6-甲基腺苷(N6-methyladenosine, m6A)位点。YTHDF2和TET2在非小细胞肺癌组织中的阳性率分别29.3%和24%，在正常组织中的阳性表达率分别为80.8%和100.0%，差异均有统计学意义(P < 0.001)。非小细胞肺癌组织中YTHDF2与肿瘤组织分化程度有关(P = 0.02)。非小细胞肺癌组织中TET2与肿瘤大小、病理类型、组织分化程度有关(P < 0.05)。非小细胞肺癌组织中YTHDF2和TET2表达呈正相关(r = 0.515, P < 0.01)。多因素Cox回归分析显示TNM分期，组织分化程度，YTHDF2表达是非小细胞肺癌预后的独立因素(P < 0.05)。结论：YTHDF2与TET2在非小细胞肺癌的进展中起一定作用，同时对于预测非小细胞肺癌的预后具有一定的意义。

Abstract: Objective: The aim of this study was to investigate the expression and clinical significance of YTH binding protein 2 (YTHDF2) and ten-eleven translocation 2 (TET2) in the NSCLC tissues. Methods: Firstly, online bioinformation tools were used to analyze RNA methylation sites of TET2, the correlation of YTHDF2 and TET2 and their prognosis values. Then, expression of YTHDF2 and TET2 were detected by immunohistochemical method in 52 NSCLC samples and normal lung tissues. The relationship between clinicopathological features was analyzed, and the correlation between the expression of YTHDF2 and TET2 was analyzed by spearman correlation. Results: There were lots of N6-methyladenosine (m6A) sites in TET2 mRNA. The positive rates of YTHDF2 and TET2 in NSCLC were 29.3% and 80.8%, respectively, and the positive expression rates in normal lung tissues were 24% and 100.0% (P < 0.001). The expression of YTHDF2 in NSCLC was significantly correlated with differentiation (P = 0.02). The expression of TET2 in NSCLC was significantly correlated with tumor size, differentiation, TNM stage (P < 0.05). There was a positive correlation between YTHDF2 and TET2 expression in NSCLC (r = 0.515, P < 0.01). Multivariate Cox regression analysis showed that the TNM stage, differentiation and YTHDF2 expression were independent prognostic factors of NSCLC (P < 0.05). Conclusion: YTHDF2 and TET2 might be involved in the progression of NSCLC and has a certain significance for predicting the prognosis of lung cancer.