研究动态
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YTHDF3作为预后预测的甲状腺癌生物标志物及其与免疫浸润的相关性

YTHDF3as a prognostic predictive biomarker of thyroid cancer and its correlation with immune infiltration.

发表日期:2023 Sep 19
作者: Yihan Zhang, Ying Chen, Ruihua Chen, Hong Zhou, Yi Lin, Bingxin Li, Huaidong Song, Guoqiang Zhou, Mei Dong, Huanbai Xu
来源: Epigenetics & Chromatin

摘要:

甲状腺癌(TC)是最常见的内分泌恶性肿瘤之一,其发病率不断上升。N6-甲基腺苷(m6A)RNA甲基化是一种重要的表观遗传修饰,是TC基因表达的重要调控因子。因此,值得研究m6A RNA甲基化调控因子在甲状腺癌(TC)中的特征和预测价值。从癌症基因组图谱(TCGA)数据库下载TC的RNA-seq数据,筛选出差异表达的调控因子。采用绝对收缩选择算子(Lasso)Cox回归构建m6A甲基化调控因子的风险模型。通过Kaplan Meier(K-M)分析和受试者工作特征(ROC)曲线评估风险评分模型的预测价值。基因集富集分析(GSEA)预测m6A甲基化调控因子在TC中的潜在机制。利用免疫组织化学(IHC)和q-PCR进行进一步验证。采用肿瘤免疫估计资源(TIMER)评估与风险相关基因和免疫浸润的相关性。IGF2BP2、YTHDF1和YTHDF3被筛选为TC的强独立预后因子。然后建立一个风险评分模型进一步筛选预测因子。最终,根据TC的总体生存(OS)结果和临床特征,筛选出YTHDF3作为潜在预测因子。同时,IHC和qPCR证实YTHDF3在TC中差异表达。YTHDF3的表达与CD4+ T细胞和巨噬细胞的浸润水平呈正相关,并与TC中的多种免疫标记物密切相关。我们证实YTHDF3可作为TC的潜在预后生物标志物。它不仅在TC的发生和发展中起关键作用,还为理解TC中m6A RNA修饰提供了新的视角。© 2023. BioMed Central Ltd., part of Springer Nature.
Thyroid cancer (TC) is one of the most common endocrine malignancies, and its morbidity continues to rise. N6-methyladenosine (m6A) RNA methylation, an epigenetic modification, is an important regulator of gene expression in TC. Therefore, it's worth finding the characteristics and predictive value of the m6A RNA methylation regulators in thyroid cancer (TC).RNA-seq data of TC was downloaded from the Cancer Genome Atlas (TCGA) database to screen out the differential expressed regulators. The absolute contraction selection operator (Lasso) Cox regression was used to construct the risk model of m6A methylation regulators. The predictive value of the risk scoring model was evaluated by Kaplan Meier (K-M) analysis and receiver operating characteristic (ROC) curves. The underlying mechanism of m6A methylation regulators in TC was predicted by gene set enrichment analysis (GSEA). Further validation was performed by using immunohistochemistry (IHC) and q-PCR. The correlation between risk-related gene and immune infiltration was evaluated by Tumour Immune Estimation Resource (TIMER).IGF2BP2, YTHDF1 and YTHDF3 were screened out as strong independent prognostic factors of TC. Then a risk score model was established to further screen the predictors. Finally, according to the results of overall survival (OS) and clinical characteristics of TC, YTHDF3 was screened out as a potential predictor. Meanwhile, IHC and qPCR confirmed that YTHDF3 was expressed differential in TC. The expression of YTHDF3 was positively associated with the infiltration level of CD4+ T cells and macrophages. It was strongly correlated with a variety of immune markers in TC.We confirmed that YTHDF3 can be used as a potential prognostic biomarker of TC. It not only plays a decisive role in the initiation and development of TC, but also provides a new perspective for understanding the modification of m6A RNA in TC.© 2023. BioMed Central Ltd., part of Springer Nature.