TNIP1 Impacts Prognosis by Modulating the Immune Microenvironment in BRCA.

Abstract

Breast invasive carcinoma (BRCA) affects women worldwide, and despite advancements in diagnosis, prevention, and treatment, outcomes remain suboptimal. TNIP1, a novel target involved in multiple immune signaling pathways, influences tumor development and survival. However, the connection between BRCA and TNIP1 remains unclear. Analysis of data from the TCGA, GEO, Sangerbox, and Ualcan databases revealed that TNIP1 is underexpressed in BRCA tissues. This finding was corroborated by RT-PCR and immunohistochemistry. Furthermore, data from the TCGA and GEPIA2 databases, along with Sangerbox, identified TNIP1 as a marker of poor prognosis in BRCA patients. TNIP1 expression shows significant positive correlations with the BRCA Tumor Microenvironment (TME) StromalScore (R = 0.22), ImmuneScore (R = 0.25), and ESTIMATEScore (R = 0.27). Various algorithms have demonstrated a strong association between TNIP1 expression and BRCA tumor-infiltrating immune cells (TIICs). Further analysis using EPIC, TIMER, MCPCounter, QUANTISEQ, xCell, and other computational tools revealed that elevated TNIP1 expression is significantly associated with increased immune cell scores. TNIP1 expression in BRCA tumor tissues also shows a strong correlation with immune checkpoint markers. Data from the HAP database indicate that TNIP1 expression is predominantly involved in the normal skin microenvironment. Subsequent analysis using the TISCH platform with the BRCA single-cell dataset demonstrated that TNIP1 exhibits higher expression levels in immune cells compared to non-immune cells in BRCA patients. This expression is significantly positively correlated with inflammation (R = 0.25) and differentiation (R = 0.28) within the TME, while showing negative correlations with BRCA stemness (R = - 0.34) and invasion (R = - 0.22). Consequently, TNIP1 is proposed as a potential prognostic marker and therapeutic target for BRCA.