ANO6 is a reliable prognostic biomarker and correlates to macrophage polarization in breast cancer.

ABSTRACT

To investigate the value of Anoctamin 6 (ANO6) in breast cancer (BC) by analyzing its expression, prognostic impact, biological function, and its association with immune characteristics. We initially performed the expression and survival analyses, followed by adopting restricted cubic spline to analyze the nonlinear relationship between ANO6 and overall survival (OS). Stratified and interaction analyses were conducted to further evaluate its prognostic value in BC. Next, we performed enrichment analyses to explore the possible pathways regulated by ANO6. Finally, the correlations between ANO6 and immune characteristics were analyzed to reveal its role in immunotherapy. Lower ANO6 expression was observed in BC than that in the normal breast group, but its overexpression independently predicted poor OS among BC patients (P < .05). Restricted cubic spline analysis revealed a linear relationship between ANO6 and OS (P-Nonlinear > 0.05). Interestingly, menopause status was an interactive factor in the correlation between ANO6 and OS (P for interaction = 0.016). Additionally, ANO6 was involved in stroma-associated pathways, and its elevation was significantly linked to high stroma scores and macrophage polarization (P < .05). Moreover, ANO6 was notably correlated with immune checkpoint expression levels, and scores of tumor mutation burden and microsatellite instability (all P < .05). ANO6 was an independent prognostic factor for BC, and might be a potential target for the BC treatment. Besides, ANO6 might affect BC progression via the regulation of stroma-related pathways and macrophage polarization.