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<p>To address the pressing need to improve breast cancer outcomes, we identify 9 plasma proteins with significant associations to breast cancer, namely ULK3, CSK, ASIP, TLR1 in breast cancer, ADH5, SARS2, ULK3, UBE2N in Luminal A subtype, PEX14 in Luminal B subtype. Tumor immune cell infiltration analysis and mutation phenotypes in mice further demonstrate a complex pattern of interaction between these genes and immune responses. Compared to normal tissues, tumor tissues exhibit reduced expression of ULK3 and CSK. Notably, elevated <i>ULK3</i> expression in both breast cancer and the Luminal A subtype is significantly associated with prolonged recurrence-free survival. Overexpression of CSK and ULK3 is confirmed to significantly inhibit the proliferation and migratory ability of MCF-7 cells. Additionally, three drug candidates—TG100801, Hydrochlorothiazide, and Imatinib—show promise in targeting these proteins, contributing valuable insights for prioritizing drug development in realm of breast cancer.</p>

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Genetic associations of plasma proteins and breast cancer identify potential therapeutic drug candidates

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月15日

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  • Liuliu Quan,
  • Xin Luo,
  • Chenxu Meng,
  • Jinsong Liu,
  • Jie Ju,
  • Zixuan Yang,
  • You Shuai,
  • Tong Wei,
  • Jiaqi Meng,
  • Peng Yuan

摘要

To address the pressing need to improve breast cancer outcomes, we identify 9 plasma proteins with significant associations to breast cancer, namely ULK3, CSK, ASIP, TLR1 in breast cancer, ADH5, SARS2, ULK3, UBE2N in Luminal A subtype, PEX14 in Luminal B subtype. Tumor immune cell infiltration analysis and mutation phenotypes in mice further demonstrate a complex pattern of interaction between these genes and immune responses. Compared to normal tissues, tumor tissues exhibit reduced expression of ULK3 and CSK. Notably, elevated ULK3 expression in both breast cancer and the Luminal A subtype is significantly associated with prolonged recurrence-free survival. Overexpression of CSK and ULK3 is confirmed to significantly inhibit the proliferation and migratory ability of MCF-7 cells. Additionally, three drug candidates—TG100801, Hydrochlorothiazide, and Imatinib—show promise in targeting these proteins, contributing valuable insights for prioritizing drug development in realm of breast cancer.