PDF(Pubmed)
Abstract：
BACKGROUND: The aim of this study was to investigate the correlation between m6A methylation regulators and cell infiltration characteristics in tumor immune microenvironment (TIME), so as to help understand the immune mechanism of early-stage lung adenocarcinoma (LUAD).
METHODS: The expression and consensus cluster analyses of m6A methylation regulators in early-stage LUAD were performed. The clinicopathological features, immune cell infiltration, survival and functional enrichment in different subtypes were analyzed. We also constructed a prognostic model. Clinical tissue samples were used to validate the expression of model genes through real-time polymerase chain reaction (RT-PCR). In addition, cell scratch assay and Transwell assay were also performed.
RESULTS: Expression of m6A methylation regulators was abnormal in early-stage LUAD. According to the consensus clustering of m6A methylation regulators, patients with early-stage LUAD were divided into two subtypes. Two subtypes showed different infiltration levels of immune cell and survival time. A prognostic model consisting of HNRNPC, IGF2BP1 and IGF2BP3 could be used to predict the survival of early-stage LUAD. RT-PCR results showed that HNRNPC, IGF2BP1 and IGF2BP3 were significantly up-regulated in early-stage LUAD tissues. The results of cell scratch assay and Transwell assay showed that overexpression of HNRNPC promotes the migration and invasion of NCI-H1299 cells, while knockdown HNRNPC inhibits the migration and invasion of NCI-H1299 cells.
CONCLUSIONS: This work reveals that m6A methylation regulators may be potential biomarkers for prognosis in patients with early-stage LUAD. Our prognostic model may be of great value in predicting the prognosis of early-stage LUAD.
METHODS: The expression and consensus cluster analyses of m6A methylation regulators in early-stage LUAD were performed. The clinicopathological features, immune cell infiltration, survival and functional enrichment in different subtypes were analyzed. We also constructed a prognostic model. Clinical tissue samples were used to validate the expression of model genes through real-time polymerase chain reaction (RT-PCR). In addition, cell scratch assay and Transwell assay were also performed.
RESULTS: Expression of m6A methylation regulators was abnormal in early-stage LUAD. According to the consensus clustering of m6A methylation regulators, patients with early-stage LUAD were divided into two subtypes. Two subtypes showed different infiltration levels of immune cell and survival time. A prognostic model consisting of HNRNPC, IGF2BP1 and IGF2BP3 could be used to predict the survival of early-stage LUAD. RT-PCR results showed that HNRNPC, IGF2BP1 and IGF2BP3 were significantly up-regulated in early-stage LUAD tissues. The results of cell scratch assay and Transwell assay showed that overexpression of HNRNPC promotes the migration and invasion of NCI-H1299 cells, while knockdown HNRNPC inhibits the migration and invasion of NCI-H1299 cells.
CONCLUSIONS: This work reveals that m6A methylation regulators may be potential biomarkers for prognosis in patients with early-stage LUAD. Our prognostic model may be of great value in predicting the prognosis of early-stage LUAD.
摘要：
背景：这项研究的目的是研究肿瘤免疫微环境（TIME）中m6A甲基化调节因子与细胞浸润特征之间的相关性，从而帮助了解早期肺腺癌(LUAD)的免疫机制。
方法：进行了早期LUAD中m6A甲基化调节因子的表达和一致性聚类分析。临床病理特征，免疫细胞浸润，分析了不同亚型的存活和功能富集。我们还构建了一个预后模子。临床组织样本用于通过实时聚合酶链反应（RT-PCR）验证模型基因的表达。此外,还进行了细胞划痕测定和Transwell测定。
结果：在早期LUAD中m6A甲基化调节因子的表达异常。根据m6A甲基化调节因子的共识聚类，早期LUAD患者分为两种亚型.两种亚型表现出不同的免疫细胞浸润水平和存活时间。由HNRNPC组成的预后模型，IGF2BP1和IGF2BP3可用于预测早期LUAD的生存。RT-PCR结果显示,HNRNPC,IGF2BP1和IGF2BP3在早期LUAD组织中显著上调。细胞划痕实验和Transwell实验结果表明,HNRNPC过表达促进NCI-H1299细胞的迁移和侵袭,而敲低HNRNPC抑制NCI-H1299细胞的迁移和侵袭。
结论：这项工作揭示了m6A甲基化调节因子可能是早期LUAD患者预后的潜在生物标志物。我们的预后模型可能对预测早期LUAD的预后具有重要价值。
方法：进行了早期LUAD中m6A甲基化调节因子的表达和一致性聚类分析。临床病理特征，免疫细胞浸润，分析了不同亚型的存活和功能富集。我们还构建了一个预后模子。临床组织样本用于通过实时聚合酶链反应（RT-PCR）验证模型基因的表达。此外,还进行了细胞划痕测定和Transwell测定。
结果：在早期LUAD中m6A甲基化调节因子的表达异常。根据m6A甲基化调节因子的共识聚类，早期LUAD患者分为两种亚型.两种亚型表现出不同的免疫细胞浸润水平和存活时间。由HNRNPC组成的预后模型，IGF2BP1和IGF2BP3可用于预测早期LUAD的生存。RT-PCR结果显示,HNRNPC,IGF2BP1和IGF2BP3在早期LUAD组织中显著上调。细胞划痕实验和Transwell实验结果表明,HNRNPC过表达促进NCI-H1299细胞的迁移和侵袭,而敲低HNRNPC抑制NCI-H1299细胞的迁移和侵袭。
结论：这项工作揭示了m6A甲基化调节因子可能是早期LUAD患者预后的潜在生物标志物。我们的预后模型可能对预测早期LUAD的预后具有重要价值。
