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Elevated ADAR expression is significantly linked to shorter overall survival and immune infiltration in patients with
Siqi Hu1, Fang Wang1, Junjun Yang1
1Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou 225001, China.
Abstract:
To date, few studies have investigated whether the RNA-editing enzymes adenosine deaminases acting on RNA (ADARs) influence RNA functioning in lung adenocarcinoma (LUAD). To investigate the role of ADAR in lung cancer, we leveraged the advantages of The Cancer Genome Atlas (TCGA) database, from which we obtained transcriptome data and clinical information from 539 patients with LUAD. First, we compared ARAR expression levels in LUAD tissues with those in normal lung tissues using paired and unpaired analyses. Next, we evaluated the influence of ADARs on multiple prognostic indicators, including overall survival at 1, 3 and 5 years, as well as disease-specific survival and progression-free interval, in patients with LUAD. We also used Kaplan-Meier survival curves to estimate overall survival and Cox regression analysis to assess covariates associated with prognosis. A nomogram was constructed to validate the impact of the ADARs and clinicopathological factors on patient survival probabilities. The volcano plot and heat map revealed the differentially expressed genes associated with ADARs in LUAD. Finally, we examined ADAR expression versus immune cell infiltration in LUAD using Spearman's analysis. Using the Gene Expression Profiling Interactive Analysis (GEPIA2) database, we identified the top 100 genes most significantly correlated with ADAR expression, constructed a protein-protein interaction network and performed a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis on these genes. Our results demonstrate that ADARs are overexpressed in LUAD and correlated with poor patient prognosis. ADARs markedly increase the infiltration of T central memory, T helper 2 and T helper cells, while reducing the infiltration of immature dendritic, dendritic and mast cells. Most immune response markers, including T cells, tumor-associated macrophages, T cell exhaustion, mast cells, macrophages, monocytes and dendritic cells, are closely correlated with ADAR expression in LUAD.
Insights
Adenosine deaminases acting on RNA (ADARs) are overexpressed in lung adenocarcinoma (LUAD), correlating with poor prognosis. ADARs influence immune cell infiltration, impacting LUAD progression and patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Adenosine deaminases acting on RNA (ADARs) are crucial RNA-editing enzymes.
- Their role in lung adenocarcinoma (LUAD) and its impact on prognosis remains underexplored.
Purpose of the Study:
- To investigate the expression levels of ADARs in LUAD tissues.
- To evaluate the association between ADAR expression and patient prognosis, including survival and progression.
- To explore the relationship between ADARs and immune cell infiltration in LUAD.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) database for transcriptome and clinical data from 539 LUAD patients.
- Performed differential expression analysis, survival analysis (Kaplan-Meier, Cox regression), and nomogram construction.
- Analyzed gene expression correlations with immune cell infiltration using Spearman's analysis and GEPIA2 database.
Main Results:
- ADARs were found to be significantly overexpressed in LUAD tissues compared to normal lung tissues.
- Higher ADAR expression correlated with poorer overall survival, disease-specific survival, and progression-free interval in LUAD patients.
- ADARs modulated the infiltration of various immune cells, increasing T cell subsets while decreasing dendritic and mast cells, and showed correlations with multiple immune response markers.
Conclusions:
- ADARs are oncogenic drivers in LUAD, associated with unfavorable patient prognosis.
- ADARs play a significant role in shaping the tumor immune microenvironment in LUAD.
- Targeting ADARs may represent a potential therapeutic strategy for LUAD.
