Spatial Transcriptomics Suggests That Alterations Occur in the Preneoplastic Breast Microenvironment of BRCA1/2...

Area of Science:

• Oncology
• Genetics
• Cell Biology

Background:

• Breast cancer is a leading cause of cancer deaths in women.
• Germline mutations in BRCA1 and BRCA2 genes significantly increase breast cancer risk.
• Defects in mammary epithelial cell differentiation occur in BRCA1/2 mutation carriers before cancer diagnosis, but mechanisms remain unclear.

Purpose of the Study:

• To investigate defects in mammary epithelial cell differentiation and microenvironmental alterations in preneoplastic breast tissues from BRCA1/2 mutation carriers.
• To explore spatial transcriptomics and receptor-ligand interactions in these tissues.

Main Methods:

• Spatial transcriptomics was employed on preneoplastic breast tissues from BRCA1/2 mutation carriers and control tissues.
• Analysis focused on receptor-ligand interactions, autocrine, and paracrine signaling.
• Differential correlation analysis of integrin-ligand pairs and integrin receptor expression in stromal cells was performed.

Main Results:

• Distinct microenvironmental alterations and cell differentiation defects were identified in BRCA1/2 mutation carriers.
• β1-integrin-mediated autocrine signaling may differ between BRCA1-deficient and BRCA2-deficient cells.
• Increased epithelial-to-stromal paracrine signaling and more differentially correlated integrin-ligand pairs were observed in BRCA1/2-mutant tissues.

Conclusions:

• Alterations in mammary epithelial cell and microenvironment communication are evident in BRCA1 and BRCA2 mutation carriers.
• These findings provide a basis for novel breast cancer chemoprevention strategies targeting high-risk populations.