Dual role of lncRNA OTUD6B-AS1 in immune evasion and ferroptosis resistance: A prognostic and therapeutic biomarker in breast cancer

Abstract

Background: Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in tumorigenesis and therapeutic resistance. This study investigates the prognostic significance and dual biological functions of lncRNA OTUD6B-AS1 in breast cancer (BC), focusing on its roles in immune evasion and ferroptosis resistance. Methods: Multi-omics data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and lncRNA databases (AnnoLnc2, LncACTdb 3.0) were integrated to analyze OTUD6B-AS1 expression, clinical relevance, and molecular networks. Experimental validations included co-culture assays with CD8+ T cells, drug sensitivity tests, and ferroptosis marker analysis. Results: OTUD6B-AS1 exhibited significant overexpression across multiple cancers, particularly in breast cancer (BC), where elevated levels strongly correlated with poor prognosis. Its expression was closely associated with key clinical indicators (T/N/M stage, ER/PR/HER2 status), prompting the development of a nomogram prognostic model with high clinical applicability. Genomic analysis revealed frequent amplification of OTUD6B-AS1 and co-occurrence of PIK3CA mutations. Co-expression and ceRNA networks highlighted its interaction with RNA degradation pathways. Notably, OTUD6B-AS1 was associated with immune evasion by regulating PD-L1 and CD8+ T cell activity. Concurrently, high OTUD6B-AS1 expression conferred ferroptosis resistance via GPX4/SLC7A11 modulation. Conclusion: In conclusion, OTUD6B-AS1 serves as a biomarker in BC, driving immune evasion and ferroptosis resistance. Targeting OTUD6B-AS1 may enhance immunotherapy efficacy and overcome chemoresistance, offering novel therapeutic avenues.

Keywords

• OTUD6B-AS1
• Breast cancer
• Prognostic model
• Ferroptosis resistance
• Immune escape