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Purpose <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>High SOD2 expression in TNBC is associated with improved outcomes and heightened immune responses, underscoring its potential as a modulator of the tumor microenvironment.</p>

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

  • 期刊论文

  • 发表日期：

    2025年7月9日

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  • Yoon Young Kim,
  • GunHee Lee,
  • Yeonjin Jeon,
  • Gyungyub Gong,
  • Kyunggon Kim,
  • JiSun Kim,
  • Byung-Kwan Jeong,
  • Hee Jin Lee

摘要

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.