Pan-Cancer Characterization of Immune-Related lncRNAs: Insights into MAGI۲-AS۳ Regulation and Therapeutic Implications in Colorectal Cancer

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 MAGI۲-AS۳ regulation and its mechanisms across different cancer types with a special focus on colorectal cancer (CRC). Methods: Building on our previous integrated systems biology study, we identified MAGI۲-AS۳ as having significant interactions with critical differentially expressed genes (DEGs) involved in cancer progression at various stages. To further elucidate its role, we conducted a comprehensive set of analyses. These included expression analyses across single cells, normal and tumor tissues, and cell lines to determine MAGI۲-AS۳ expression patterns. We performed functional correlation and enrichment analyses to understand its biological significance. Survival analyses, including Kaplan-Meier curves and Cox regression, were used to assess the prognostic value of MAGI۲-AS۳. We also examined immune infiltration, immune-related pathways, immuno-modulatory effects, and responses to immunotherapy to uncover the immune landscape associated with MAGI۲-AS۳. Additionally, we carried out a pan-cancer analysis of drug sensitivity, investigated genomic alterations, and conducted methylation analysis at the pan-cancer level to provide a holistic view of MAGI۲-AS۳'s involvement in cancer biology. Results: Our findings revealed that MAGI۲-AS۳ exhibited high expression in several cancer types, while showing low expression in others, with differential expression observed across various cell lines and single-cell populations. Functional enrichment analyses indicated that MAGI۲-AS۳ is significantly involved in cancer-related pathways, including cellular motility, signal transduction, and immune regulation. Survival analyses demonstrated that MAGI۲-AS۳ holds significant prognostic value for multiple clinical endpoints, such as overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and relapse-free survival (RFS). Immune analysis revealed both positive and negative correlations with different immune system components and significant impacts on immune pathway functions in a pan-cancer context. In CRC, MAGI۲-AS۳ showed strong correlations with various immunomodulators and its dysregulated expression was significantly associated with responses to immune checkpoint inhibitors. Furthermore, MAGI۲-AS۳ expression was notably significant in terms of drug sensitivity and resistance, particularly in CRC, when related to common anticancer small molecules. Pan-cancer analysis of MAGI۲-AS۳ s mutational and methylation profiles indicated a low degree of amplification and deep deletions, as well as gain and loss of function mutations, affecting the expression of numerous downstream genes. These alterations were linked to differential promoter methylation across various cancer types. Conclusion: Our study positions MAGI۲-AS۳ 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 MAGI۲-AS۳ in cancer treatment.

کلیدواژه ها:

MAGI۲-AS۳ ، Immunotherapy ، Immune infiltration ، Prognosis ، Pan-cancer