Reticulon 4 in Breast Cancer: A Comprehensive Analysis of its Biomarker Potential for Prognosis, Immunology, and Drug Sensitivity

Abstract Breast cancer (BC), the most prevalent cancer among women, necessitates the identification of effective early detection biomarkers. Reticulon 4 (RTN4), a neurite growth inhibitor primarily expressed in the central nervous system, has recently been implicated in cancer development. This study aimed to comprehensively examine the expression level, prognostic and immunological value, function and drug sensitivity of RTN4 in BC. Expression and survival analyses were performed using HPA, TIMER, GEPIA, UALCAN, and PROGgeneV2; immune-related features were explored via TISIDB, TIMER, and Sangerbox, while drug sensitivity analysis was conducted using the CellMiner database. RTN4 expression was observed significantly lower in BC compared to the normal tissues (p<0.05). Elevated mRNA expression levels of RTN4 were significantly associated with shorter overall survival in BC patients (p<0.05). Analysis of the tumor microenvironment (TME) revealed significant correlations between RTN4 and immune cell infiltration, immune and molecular subtypes, and stromal components (p<0.05). Furthermore, microsatellite instability, most immunomodulatory genes, and nearly half of immune checkpoints in BC showed significant associations with RTN4 expression (p<0.05). In addition, its expression showed significant correlations with the drug sensitivities of lovastatin, simvastatin, and fluvastatin (p<0.05). Considering its differential expression and significant correlation with BC prognosis, TME, and immune-related genes, RTN4 shows promise as a potential biomarker candidate, offering guidance for innovative treatment approaches for BC.