2. Academic Validation
  3. Gene signatures associated with brain-topical proliferative activity in breast cancer

Gene signatures associated with brain-topical proliferative activity in breast cancer

  • Biochem Biophys Res Commun. 2025 Aug 15:775:152127. doi: 10.1016/j.bbrc.2025.152127.
Yuka Kuroiwa 1,  Yuta Doi 2,  Kazuya Nakamichi 3,  Yusuke Yamamoto 4,  Kentaro Semba 5
Affiliations

Affiliations

  • 1 Laboratory of Integrative Oncology, National Cancer Center Research Institute, Tokyo, Japan; Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan. Electronic address: [email protected].
  • 2 Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
  • 3 Laboratory of Integrative Oncology, National Cancer Center Research Institute, Tokyo, Japan; Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
  • 4 Laboratory of Integrative Oncology, National Cancer Center Research Institute, Tokyo, Japan.
  • 5 Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan; Translational Research Center, Fukushima Medical University, Fukushima, Japan. Electronic address: [email protected].
PMID: 40466362 DOI: 10.1016/j.bbrc.2025.152127
Abstract

Breast Cancer is a type of Cancer with relatively good prognosis; however, once it metastasizes to the brain, it deteriorates clinical outcomes. Previously, we compared the brain-topical proliferative activity of multiple breast Cancer cell lines by intracranial injection and identified UACC-893 cells as highly proliferative in the brain. In this study, we performed RNA-seq analysis of brains harboring UACC-893 tumors and explored the genes characteristically expressed in tumor cells colonizing the brain and in their surrounding brain tissue. Enrichment analysis suggested that immune-related signals may be involved in the brain-topical proliferative activity of tumor cells. In addition, ligand-coding genes were extracted among those characteristically expressed in the intracranial tumor or in the brain containing it. This result was validated by quantitative Real-Time PCR analysis. NicheNet analysis using RNA-seq data suggested the interaction between tumor cells and the brain microenvironment, which suggested possible communications via the ligand-receptor axis. In summary, this study highlights the genes and signals characteristic of highly proliferative tumor cells and the affected brain tissue influencing tumor colonization.

Keywords

Brain metastasis; HER2-Positive breast cancer; RNA sequencing; Xenome; in vivo.

Figures