Nuclear expression of AIRE in lung squamous cell carcinoma correlates with immune microenvironment remodeling and poor prognosis

Abstract

Objective:

The autoimmune regulator (AIRE), an atypical transcriptional regulator, exhibits aberrant expression in multiple tumor types. However, its significance in lung squamous cell carcinoma (LUSC) is still uncertain. This study investigated AIRE’s expression, immune microenvironment association, and prognostic value in LUSC.

Method:

AIRE expression was analyzed using TCGA database, validated via RT-qPCR/Western blot in LUSC (H1703, SK-MES-1, EBC-1) vs. normal (BEAS-2B) cells. Tissue microarray immunohistochemistry (IHC) quantified nuclear/cytoplasmic AIRE in clinical samples. Clinicopathological correlations, immune infiltration (CIBERSORT), and survival outcomes were assessed. A nomogram integrating nuclear AIRE and clinical factors predicted 1/3/5-year survival (C-index evaluation).

Result:

AIRE was upregulated in LUSC. Nuclear AIRE was tumor-specific (absent in normal tissue), elevated in inflammatory stroma (6.29 ± 4.57 vs. 3.10 ± 3.66, P < 0.001), and correlated with lymphocyte infiltration (R = 0.437, P < 0.001). High AIRE linked to increased Tregs (P< 0.001) and reduced dendritic cells (P< 0.01). No association with age, stage, or Ki-67 (P > 0.05) was observed. Patients with high AIRE had worse survival (HR = 2.00 [1.02 - 3.93], P = 0.043). The nomogram incorporating nuclear AIRE achieved a C-index of 0.814 for outcome estimation in our cohort.

Conclusion:

In a LUSC cohort, nuclear AIRE expression is associated with immune microenvironment features and poorer overall survival. However, its incremental prognostic value beyond established clinicopathological variables appears modest, and further external validation and functional studies are warranted.