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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1522149
This article is part of the Research Topic Integrating Molecular Mechanisms, Immunotherapy, and Drug Sensitivity in Cancer Immunology and Oncology View all 15 articles

Carboplatin-resistance-related DNA damage repair prognostic gene signature and its association with immune infiltration in breast cancer

Provisionally accepted
Shuwen Dong Shuwen Dong Anqi Li Anqi Li Ruixin Pan Ruixin Pan Jin Hong Jin Hong Zheng Wang Zheng Wang *Kunwei Shen Kunwei Shen
  • Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

The final, formatted version of the article will be published soon.

    Breast cancer is among the most prevalent malignant tumors globally, with carboplatin serving as a standard treatment option. However, resistance often compromises its efficacy. DNA damage repair (DDR) pathways are crucial in determining responses to treatment and are also associated with immune infiltration. This study aimed to identify the DDR genes involved in carboplatin resistance and to elucidate their effects on prognosis, immune infiltration, and drug sensitivity in breast cancer patients. We constructed the 3D-culture model of the MDA-MB-231 cell line, both resistant and sensitive to carboplatin, and identified a set of DDR genes. By integrating data from a public database, we established a prognostic signature comprising thirteen DDR genes. Our analysis indicated that this model is associated with immune infiltration patterns in breast cancer patients, particularly concerning CD8+ T cells and NK cells. Additionally, it demonstrated a significant correlation with sensitivity to other DDR-related drugs, suggesting its potential as a biomarker for treatment efficacy. Compared to the control group, TONSL-knockdown cell lines exhibited a diminished response to DNA-damaging agents, marked by a notable increase in DNA damage levels and enhanced drug sensitivity. Furthermore, single-cell analysis revealed elevated TONSL expression in dendritic and epithelial cells, particularly in triple-negative breast cancers.

    Keywords: breast cancer, Carboplatin resistance, DNA repair genes, Immune infiltration, TONSL

    Received: 04 Nov 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Dong, Li, Pan, Hong, Wang and Shen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zheng Wang, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

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