Investigating the prognostic role of citrullination-related genes in breast cancer by combining transcriptomics, single-cell analysis and verification

  • 0Department of Radiation Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China; Department of Oncology, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China; State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Medical University, Nanning, Guangxi, 530021, China.

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Summary

This summary is machine-generated.

This study identifies four key citrullination-related genes (CRGs) — SEZ6, S100B, SPIB, and TFF1 — that predict prognosis in breast cancer (BRCA). These genes also correlate with the tumor immune microenvironment, offering potential therapeutic targets.

Area Of Science

  • Oncology
  • Immunology
  • Genetics

Background

  • Citrullination is linked to autoimmune diseases and implicated in cancer, but its specific role in breast cancer (BRCA) prognosis is not well understood.
  • Identifying prognostic biomarkers is crucial for improving breast cancer patient outcomes and developing targeted therapies.

Purpose Of The Study

  • To identify citrullination-related genes (CRGs) that are associated with prognosis in breast cancer (BRCA).
  • To develop a prognostic model based on identified CRGs and explore their relationship with the tumor immune microenvironment (TME).

Main Methods

  • Utilized The Cancer Genome Atlas (TCGA-BRCA) and Gene Expression Omnibus (GEO) datasets to identify differentially expressed genes (DEGs) and intersect them with known CRGs.
  • Employed univariate and Lasso Cox regression for CRG selection, followed by multivariate Cox regression to build a prognostic nomogram.
  • Analyzed the correlation between CRGs, TME characteristics (e.g., immune cell infiltration, immune subtypes), and PD-L1 expression.

Main Results

  • Identified SEZ6, S100B, SPIB, and TFF1 as key CRGs for constructing a prognostic risk model in BRCA.
  • High-risk BRCA patients showed an immunosuppressive TME with low CD8+ T cell infiltration, while low-risk patients had higher immune infiltration.
  • Specific CRGs correlated with distinct immune cell infiltration patterns (NK cells, T cells, neutrophils) and PD-L1 expression.

Conclusions

  • SEZ6, S100B, SPIB, and TFF1 are significant prognostic genes in BRCA, offering insights into disease pathogenesis.
  • The identified CRGs are associated with the tumor immune microenvironment, suggesting potential for immunomodulatory therapeutic strategies in BRCA.
  • This study provides a foundation for developing personalized treatment strategies for breast cancer based on CRG expression and immune profiles.