MECOM/PRDM3 and PRDM16 Serve as Prognostic-Related Biomarkers and Are Correlated With Immune Cell Infiltration in Lung Adenocarcinoma.

Na Liu,Yanpeng Zhang,Meng Fan,Puyu Shi,Tian Yang,Ke Wang,Hui Ren,Mingwei Chen,Meng Li

doi:10.3389/fonc.2022.772686

Abstract

BackgroundThe 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.MethodsThe 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.ResultsmRNA 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.ConclusionMECOM and PRDM16 may serve as potential prognostic biomarkers which govern immune cell recruitment to LUAD.

Highlights

Lung cancer, a malignant disease, poses a serious threat to human health, especially in East Asia [1]
Results: mRNA levels of MDS1 and EVI1 complex locus (MECOM) and PR domain containing 16 (PRDM16) were downregulated in lung adenocarcinoma (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 may serve as potential prognostic biomarkers which govern immune cell recruitment to LUAD

Summary

Introduction

A malignant disease, poses a serious threat to human health, especially in East Asia [1]. Despite the advances in lung cancer-related treatment technology, the longtime survival remains poor, with a 5-year survival rate of less than 20% [5]. MECOM and PRDM16 are the most mutated genes in the PRDM family in multiple human cancers [12, 13], which has been verified to promote the occurrence and progression of acute myeloid leukemia [14, 15]. The potential mechanism of MECOM and PRDM16, especially MECOM, in terms of tumor progression, prognosis, and immune cell infiltration in LUAD, remains unclear. The MDS1 and EVI1 complex locus (MECOM, called PRDM3) and PR domain containing 16 (PRDM16) are two highly related zinc finger transcription factors associated with many malignancies. The mechanisms of MECOM and PRDM16 in prognosis and tumor immune infiltration in lung adenocarcinoma (LUAD) remain uncertain

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Results

Conclusion