Pan-Cancer Insights into HAND۲-AS۱ LncRNA: Tumor Suppressor, Prognostic Biomarker, and Immunotherapeutic Target

HAND۲-AS۱ (HAND۲ Antisense RNA ۱), a long noncoding RNA (lncRNA), plays a crucial role in the initiation of various cancer types, highlighting its significant involvement in cancer processes and immune responses. To gain deeper insights into HAND۲-AS۱’s functional nuances and identify novel avenues for cancer immunotherapy, we conducted a comprehensive evaluation of this gene. Methods: Our approach involved synergistic network analysis and the construction of lncRNA-mRNA interacting genes. Through this, we introduce HAND۲-AS۱ and emphasize its key roles in tumorigenesis and immune regulation. First, we identified key targets by constructing the DEGs/DE-lncRNA regulatory network and performed functional enrichment analysis. Additionally, we evaluated HAND۲-AS۱ expression levels in different cancers and measured its prognostic impact. Furthermore, we investigated immune system penetration, immune-related pathway analysis, DNA methylation, and mutation profiles. Finally, we clinically validated HAND۲-AS۱ using CRC tumor and normal samples. Results: The results span ۳۳ distinct cancer types, revealing aberrant HAND۲-AS۱ expression patterns, methylation changes, mutational signatures, and immune involvement. Notably, HAND۲-AS۱ tends to be down-regulated in most tumors, significantly correlating with poor survival outcomes. Functional enrichment analysis suggests HAND۲-AS۱’s involvement in tumor progression and its association with diverse immune pathways across different tumor classifications. Moreover, HAND۲-AS۱ expression positively correlates with key immune cell infiltration, including immunosuppressive agents (e.g., tumor-associated macrophages, cancer-associated fibroblasts, and Tregs) and immune effector cells (such as NK and CD۸+ T cells) in a pan-cancer context. Conclusion: Overall, our findings extend beyond the molecular landscape of colorectal cancer (CRC), highlighting HAND۲-AS۱’s pivotal role in complex immune pathways. Altered methylation and mutation patterns across various cancer types underscore HAND۲-AS۱ as a critical driver of cancer progression. Its ability to modulate immune components and influence immune-related pathways not only informs diagnosis but also holds promise for immune-based therapeutic strategies against cancer. HAND۲-AS۱ emerges as a multifaceted switch, offering insights into cancer development, progression, and potential diagnostic accuracy.

کلیدواژه ها:

HAND۲-AS۱ ، pan-cancer ، prognostic biomarker ، immunotherapy ، immune analysis