SOD2 expression in patients with triple-negative breast cancer is associated with tumor-infiltrating lymphocytes and prognosis.

Purpose: Superoxide dismutase 2 (SOD2), an antioxidant enzyme, plays a pivotal role in carcinogenesis and immune regulation. In this study, we investigated the expression and implications of superoxide dismutase (SOD2) in triple-negative breast cancer (TNBC), an aggressive subtype with varying immune profiles and clinical outcomes.

Methods: Multiple TNBC cohorts were analyzed with various methodologies including immunohistochemistry (IHC), proteomics, and RNA expressions. Immunostaining of SOD2 with tissue microarrays from 229 surgical samples and 144 pre-neoadjuvant chemotherapy biopsy samples were performed. Four hundred three formalin-fixed and paraffin-embedded samples underwent deparaffinization for protein extraction and three hundred thirty-six samples remained after quality control. Ninety-one TNBC samples from The Cancer Genome Atlas data and five hundred thirty-four TNBC samples from public database were also analyzed.

Results: We identified positive correlations between SOD2 expression and immune-related genes, as well as tumor-infiltrating lymphocytes (TILs) levels, while observing negative associations with fibrosis-related pathways. Immunohistochemical analysis further supported the positive correlation between SOD2 and immune response. Furthermore, elevated SOD2 expression predicted favorable survival outcomes in patients with TNBC. Notably, analysis of single-cell RNA-seq data revealed increased SOD2 expression in cancer-associated fibroblasts associated with higher TILs levels, enhanced inflammatory signaling, and reduced fibrogenesis.

Conclusion: High SOD2 expression in TNBC is associated with improved outcomes and heightened immune responses, underscoring its potential as a modulator of the tumor microenvironment.