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Abstract：
BACKGROUND: The MDS1 and EVI1 complex locus (MECOM, also called PRDM3) and PR domain containing 16 (PRDM16) are two highly related zinc finger transcription factors associated with many malignancies. However, the mechanisms of MECOM and PRDM16 in prognosis and tumor immune infiltration in lung adenocarcinoma (LUAD) remain uncertain.
METHODS: The Cancer Genome Atlas (TCGA), Oncomine, UALCAN, GEPIA, and TIMER databases were searched to determine the relationship between the expression of MECOM and PRDM16, clinicopathological features, immune infiltration, and prognosis in LUAD. Coexpressed genes of the two genes were investigated by CBioPortal, and the potential mechanism of MECOM- and PRDM16-related genes was elucidated by GO and KEGG analyses. STRING database was utilized to further construct the protein-protein interaction network of the coexpressed genes, and the hub genes were identified by Cytoscape. Finally, qRT-PCR was performed to identify the mRNA levels of the target genes in LUAD.
RESULTS: mRNA levels of MECOM and PRDM16 were downregulated in LUAD (p < 0.05), and the low expression of the two genes was associated with the age, gender, smoking duration, tissue subtype, poor stage, nodal metastasis status, TP53 mutation, and prognosis in LUAD (p < 0.05). MECOM and PRDM16 were also found to be correlated with the expression of a variety of immune cell subsets and their markers. KEGG analysis showed that both of them were mainly enriched in the cell cycle, cellular senescence, DNA replication, and p53 signaling pathway. Importantly, the mRNA levels of the two genes were also found to be decreased in the clinical samples of LUAD by qRT-PCR.
CONCLUSIONS: MECOM and PRDM16 may serve as potential prognostic biomarkers which govern immune cell recruitment to LUAD.
METHODS: The Cancer Genome Atlas (TCGA), Oncomine, UALCAN, GEPIA, and TIMER databases were searched to determine the relationship between the expression of MECOM and PRDM16, clinicopathological features, immune infiltration, and prognosis in LUAD. Coexpressed genes of the two genes were investigated by CBioPortal, and the potential mechanism of MECOM- and PRDM16-related genes was elucidated by GO and KEGG analyses. STRING database was utilized to further construct the protein-protein interaction network of the coexpressed genes, and the hub genes were identified by Cytoscape. Finally, qRT-PCR was performed to identify the mRNA levels of the target genes in LUAD.
RESULTS: mRNA levels of MECOM and PRDM16 were downregulated in LUAD (p < 0.05), and the low expression of the two genes was associated with the age, gender, smoking duration, tissue subtype, poor stage, nodal metastasis status, TP53 mutation, and prognosis in LUAD (p < 0.05). MECOM and PRDM16 were also found to be correlated with the expression of a variety of immune cell subsets and their markers. KEGG analysis showed that both of them were mainly enriched in the cell cycle, cellular senescence, DNA replication, and p53 signaling pathway. Importantly, the mRNA levels of the two genes were also found to be decreased in the clinical samples of LUAD by qRT-PCR.
CONCLUSIONS: MECOM and PRDM16 may serve as potential prognostic biomarkers which govern immune cell recruitment to LUAD.
摘要：
背景：MDS1和EVI1复合物基因座（MECOM，也称为PRDM3）和含PR结构域16（PRDM16）是两种与许多恶性肿瘤相关的高度相关的锌指转录因子。然而,MECOM和PRDM16在肺腺癌（LUAD）预后和肿瘤免疫浸润中的作用机制尚不明确。
方法：癌症基因组图谱（TCGA），Oncomine,UALCAN,GEPIA,和TIMER数据库进行搜索，以确定MECOM和PRDM16的表达之间的关系，临床病理特征，免疫浸润，和LUAD的预后。CBioPortal研究了这两个基因的共表达基因，并通过GO和KEGG分析阐明了MECOM和PRDM16相关基因的潜在机制。利用STRING数据库进一步构建共表达基因的蛋白质-蛋白质相互作用网络，中心基因由Cytoscape鉴定。最后,进行qRT-PCR以鉴定LUAD中靶基因的mRNA水平。
结果：LUAD中MECOM和PRDM16的mRNA水平下调（p<0.05），这两个基因的低表达与年龄有关，性别,吸烟持续时间,组织亚型,可怜的舞台，淋巴结转移状态，TP53突变,和LUAD的预后（p<0.05）。还发现MECOM和PRDM16与多种免疫细胞亚群及其标志物的表达相关。KEGG分析显示两者主要富集在细胞周期,细胞衰老,DNA复制,和p53信号通路。重要的是,通过qRT-PCR还发现这两个基因的mRNA水平在LUAD的临床样品中降低。
结论：MECOM和PRDM16可能作为潜在的预后生物标志物，控制免疫细胞募集到LUAD。
方法：癌症基因组图谱（TCGA），Oncomine,UALCAN,GEPIA,和TIMER数据库进行搜索，以确定MECOM和PRDM16的表达之间的关系，临床病理特征，免疫浸润，和LUAD的预后。CBioPortal研究了这两个基因的共表达基因，并通过GO和KEGG分析阐明了MECOM和PRDM16相关基因的潜在机制。利用STRING数据库进一步构建共表达基因的蛋白质-蛋白质相互作用网络，中心基因由Cytoscape鉴定。最后,进行qRT-PCR以鉴定LUAD中靶基因的mRNA水平。
结果：LUAD中MECOM和PRDM16的mRNA水平下调（p<0.05），这两个基因的低表达与年龄有关，性别,吸烟持续时间,组织亚型,可怜的舞台，淋巴结转移状态，TP53突变,和LUAD的预后（p<0.05）。还发现MECOM和PRDM16与多种免疫细胞亚群及其标志物的表达相关。KEGG分析显示两者主要富集在细胞周期,细胞衰老,DNA复制,和p53信号通路。重要的是,通过qRT-PCR还发现这两个基因的mRNA水平在LUAD的临床样品中降低。
结论：MECOM和PRDM16可能作为潜在的预后生物标志物，控制免疫细胞募集到LUAD。
