Novel p53-related lncRNAs as immune-associated biomarkers in colorectal cancer

Abstract

BackgroundThe p53 signaling pathway plays a critical role in colorectal cancer (CRC) development and progression. However, the contribution of p53-associated long noncoding RNAs (lncRNAs) to tumor biology and their potential clinical relevance remain insufficiently understood. This study aimed to identify clinically relevant p53-related lncRNAs and evaluate their diagnostic and immune-associated significance in CRC.MethodsRNA sequencing and clinical data from 483 CRC and 41 normal tissues in TCGA-COAD, along with independent GEO datasets (GSE39582 and GSE128449), were analyzed to identify differentially expressed genes and noncoding RNAs. Prognostic relevance was assessed using Cox regression analysis. Associations with tumor immune infiltration were evaluated using computational immune estimation methods. A regulatory interaction network was constructed to identify key lncRNAs. Expression levels of selected candidates were validated by quantitative real-time PCR in 25 paired CRC and adjacent normal tissues.ResultsSeventy-four p53-associated genes were consistently dysregulated across datasets. Network integration highlighted two lncRNAs, MIR23AHG and MIRLET7BHG, as central regulatory candidates. Both were significantly upregulated in CRC tissues and demonstrated moderate-to-good diagnostic performance (AUC = 0.80 and 0.77, respectively). Survival analysis identified CD82, CDKN2A, and INHBB as risk-associated genes. The identified p53-related signature showed significant correlations with immune cell infiltration, particularly CD4(+) T cells, dendritic cells, and B cells. qPCR validation confirmed marked overexpression of MIR23AHG and MIRLET7BHG in clinical CRC samples.ConclusionMIR23AHG and MIRLET7BHG are novel p53-associated lncRNAs that show promising diagnostic potential and immune-related relevance in CRC. While not proposed as standalone clinical markers, these lncRNAs may serve as complementary molecular biomarkers and warrant further functional and prospective clinical validation.