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Background <p>Breast cancer (BRCA) remains a leading cause of cancer-related mortality among women worldwide. The kinesin family member 5B (KIF5B) has been implicated in various cancers, yet its comprehensive role in BRCA prognosis, tumor microenvironment (TME), and therapeutic response remains poorly understood.</p> Methods <p>We integrated single-cell RNA sequencing (scRNA-seq) data and bulk RNA-seq data from multiple datasets. Using hdWGCNA, we identified gene modules related to the unfolded protein response (UPR). Consensus clustering defined UPR-related molecular subtypes, and differential expression analysis revealed key prognostic genes. KIF5B was further evaluated for its prognostic significance, mutational landscape, immune infiltration associations, and potential as a therapeutic target.</p> Results <p>Malignant cell-specific KIF5B upregulation drives poor overall survival in pan-cancer cohorts, validating its hazardous molecular function. Functional enrichment analysis linked KIF5B to critical pathways, including immune response, JAK-STAT signaling, and epithelial-mesenchymal transition. Immune infiltration analysis revealed that high KIF5B expression was associated with reduced immune and ESTIMATE scores, but higher tumor purity. Drug sensitivity prediction identified several compounds with potential efficacy in high KIF5B-expressing patients, including Sapitinib and LCL161.</p> Conclusion <p>Our multimodal analysis establishes KIF5B as a prognostic biomarker and potential therapeutic target in BRCA, with implications for understanding immune evasion and guiding precision treatment strategies.</p>

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KIF5B-driven unfolded protein response reprograms breast cancer immunosuppressive microenvironment for single-cell guided therapeutic targeting

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月26日

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  • Yue Liu,
  • Shuyu Li,
  • Zhiyong Luo,
  • Yun Xia,
  • Panshi Zhang

摘要

Background

Breast cancer (BRCA) remains a leading cause of cancer-related mortality among women worldwide. The kinesin family member 5B (KIF5B) has been implicated in various cancers, yet its comprehensive role in BRCA prognosis, tumor microenvironment (TME), and therapeutic response remains poorly understood.

Methods

We integrated single-cell RNA sequencing (scRNA-seq) data and bulk RNA-seq data from multiple datasets. Using hdWGCNA, we identified gene modules related to the unfolded protein response (UPR). Consensus clustering defined UPR-related molecular subtypes, and differential expression analysis revealed key prognostic genes. KIF5B was further evaluated for its prognostic significance, mutational landscape, immune infiltration associations, and potential as a therapeutic target.

Results

Malignant cell-specific KIF5B upregulation drives poor overall survival in pan-cancer cohorts, validating its hazardous molecular function. Functional enrichment analysis linked KIF5B to critical pathways, including immune response, JAK-STAT signaling, and epithelial-mesenchymal transition. Immune infiltration analysis revealed that high KIF5B expression was associated with reduced immune and ESTIMATE scores, but higher tumor purity. Drug sensitivity prediction identified several compounds with potential efficacy in high KIF5B-expressing patients, including Sapitinib and LCL161.

Conclusion

Our multimodal analysis establishes KIF5B as a prognostic biomarker and potential therapeutic target in BRCA, with implications for understanding immune evasion and guiding precision treatment strategies.