| 王月帆,葛春梅,尹昊瓒,戴智慧,董峻鹏,季 曼,李 雯,杨 富.m6A甲基化修饰识别蛋白YTHDF2在肝癌组织中的表达及临床意义[J].,2021,(9):1601-1606 |
| m6A甲基化修饰识别蛋白YTHDF2在肝癌组织中的表达及临床意义 |
| Expression and Clinical Significance of m6A Binding-Protein YTHDF2 in Hepatocellular Carcinoma |
| 投稿时间：2020-11-23 修订日期：2020-12-18 |
| DOI：10.13241/j.cnki.pmb.2021.09.001 |
| 中文关键词: 肝癌 m6A甲基化修饰 YTHDF2：临床预后 |
| 英文关键词: Hepatocellular carcinoma M6A methylation modification YTHDF2 Prognosis |
| 基金项目:国家重点研发计划项目(2016YFC1302303)；国家自然科学基金项目(81972657；81672345) |
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| 中文摘要: |
| 摘要 目的：探讨m6A甲基化修饰结合蛋白YTHDF2(YTH domain-containing family protein 2)在肝癌（Hepatocellular carcinoma, HCC）组织中的表达及临床意义。方法：1）采用Western blot和实时荧光定量PCR（Quantitative Real Time PCR, qRT-PCR）检测20对肝癌和癌旁组织中YTHDF2在蛋白和mRNA水平的表达情况。2）通过免疫组织化学（Immunochemistry, IHC）检测40对肝癌和癌旁组织芯片YTHDF2的表达情况，并以H-score评分法进行半定量分析。3）通过基因表达谱数据动态分析数据库GEPIA（http://gepia.cancer-pku.cn/）分析YTHDF2在肝癌组织中的表达及对患者生存预后的影响；通过肿瘤免疫评估资源数据库TIMER(https://cistrome.shinyapps.io/timer/)分析YTHDF2与肝癌免疫微环境的相关性。结果：相比于癌旁肝组织，YTHDF2在肝癌组织中蛋白和mRNA水平均显著高表达（P＜0.05）；GEPIA数据库分析验证：YTHDF2肝癌组织表达水平高于正常肝组织，且YTHDF2在肝癌不同分期中表达水平均高于正常肝组织（P=0.0206），Stage III期最为明显；YTHDF2高表达患者的总体生存率（Overall Survival，OS）和无复发生存率（Disease Free Survival, DFS）均较差（P=0.00027和P=0.013）；TIMER数据库分析表明：YTHDF2在肝癌免疫微环境中与各类免疫细胞呈正相关（P＜0.05），但肝癌患者的累积存活率不受免疫细胞的影响（P＞0.05），YTHDF2高表达对患者的生存预后具有不良影响（P=0.007）。结论：YTHDF2在肝癌组织中显著高表达，且YTHDF2高表达水平对肝癌患者生存预后具有不良影响，YTHDF2可作为肝癌临床预后判断的分子标志物，为今后肝癌治疗靶点提供新的策略。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the expression and clinical significance of m6A methylated modification binding protein YTHDF2 (YTH domain-containing family protein 2) in hepatocellular carcinoma (HCC). Methods: 1) The protein and mRNA expression of YTHDF2 in 20 pairs of HCC tissue and para-cancer tissue was detected by western blot and quantitative real-time PCR (qRT-PCR). 2) The expression of YTHDF2 in microarray with 40 pairs of HCC tissue and para-tumor tissue was detected by immunochemistry. H-score was used for semi-quantitative analysis. 3) The expression of YTHDF2 in HCC as well as its influence on survival prognosis of patients were analyzed by the GEPIA database (http://gepia.cancer-pku.cn/); The correlation between YTHDF2 and tumor immune microenvironment was analyzed by the TIMER database (https://cistrome.shinyapps.io/timer/). Results: The protein and mRNA expression of YTHDF2 in HCC was significantly higher than that in para-tumor tissue (P<0.05). GEPIA analysis verified that the expression of YTHDF2 in HCC was higher than that in normal liver tissue; the expression of YTHDF2 in different stages of HCC was also higher than that in normal liver tissue (P=0.0206), which was most obvious at Stage III. The overall survival (OS) and disease-free survival (DFS) of patients with high YTHDF2 expression were poor (P=0.00027 and P=0.013). TIMER database analysis showed that YTHDF2 was positively correlated with various types of immune cells in the immune microenvironment of HCC (P<0.05), but cumulative survival of HCC patients was not affected by immune cells (P>0.05), and the overexpression of YTHDF2 had a negative influence on the survival prognosis of patients (P=0.007). Conclusion: YTHDF2 was obviously overexpressed in HCC tissue. The overexpression of YTHDF2 had an adverse effect on the survival prognosis of HCC patients, suggesting that YTHDF2 may be a predictive molecular marker for clinical prognosis of HCC and providing a new strategy for therapeutic targets of HCC in the future. |
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