Comprehensive analysis of long non-coding RNA MAGI2-AS3 as a key immune regulator, therapeutic target and prognostic biomarker across pan-cancer with a focus on colorectal cancer
Authors: Maghool Fatemeh , Mohammadzadeh Samaneh , Heidari Aida , Samadi Pouria 
Published: August 2024

Abstract

Background
Long noncoding RNAs (lncRNAs) are increasingly recognized as essential regulators of gene expression, playing crucial roles in various cancer pathways, including initiation, progression, and immune regulation. However, the clinical significance of immune-related lncRNAs remains largely unexplored. This study comprehensively examines the landscape of lncRNA MAGI2-AS3 regulation and its mechanisms across different cancer types with a special focus on colorectal cancer (CRC).
Methods:
Building on previous integrated systems biology research, the study identified MAGI2-AS3 as significantly interacting with differentially expressed genes (DEGs) critical in cancer progression across various stages. To further investigate MAGI2-AS3's role, a comprehensive set of analyses was conducted. Expression patterns of MAGI2-AS3 were examined across single cells, normal and tumor tissues, and cell lines. Functional correlation and enrichment analyses were performed to elucidate its biological significance. Prognostic value was assessed through survival analyses, including Kaplan-Meier curves and Cox regression. The study also explored immune infiltration, immune-related pathways, immunomodulatory effects, and responses to immunotherapy to understand the immune landscape associated with MAGI2-AS3. Additionally, a pan-cancer analysis of drug sensitivity, genomic alterations, and methylation was conducted to provide a holistic view of MAGI2-AS3's involvement in cancer biology.
Results:
The study found that MAGI2-AS3 exhibited variable expression across different cancer types, with high expression in some cancers and low in others, including differential expression in various cell lines and single-cell populations. Functional enrichment analyses showed that MAGI2-AS3 is significantly involved in cancer-related pathways such as cellular motility, signal transduction, and immune regulation. Survival analyses revealed that MAGI2-AS3 has significant prognostic value for clinical endpoints like overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and relapse-free survival (RFS). Immune analysis indicated both positive and negative correlations with different immune system components, affecting immune pathway functions in a pan-cancer context. In colorectal cancer (CRC), MAGI2-AS3 showed strong correlations with various immunomodulators and its dysregulated expression was significantly associated with responses to immune checkpoint inhibitors. Additionally, MAGI2-AS3 expression was linked to drug sensitivity and resistance, especially in CRC, concerning common anticancer small molecules. Pan-cancer analysis of MAGI2-AS3's mutational and methylation profiles revealed low degrees of amplification and deep deletions, gain and loss of function mutations, and differential promoter methylation, affecting the expression of numerous downstream genes across various cancer types.
Conclusion:
Our study positions MAGI2-AS3 as a versatile and potent biomarker with significant implications for cancer prognosis and therapy. Its role as an immune regulator and its impact on drug sensitivity make it a promising candidate for developing advanced therapeutic strategies, particularly in colorectal cancer. Further research and clinical validation are warranted to fully harness the potential of MAGI2-AS3 in cancer treatment.