Spatial Mapping of the Precancer-to-Cancer Transition in Breast and Prostate.

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Breast and prostate cancers are hormone-driven adenocarcinomas with similar invasion pathways.
• Understanding the precancerous to invasive transition is crucial for developing targeted therapies.

Purpose of the Study:

• To identify gene-expression features and structural insights defining the shift from precancer to invasive disease in breast and prostate cancers.
• To explore the role of specific genes and immune cells in cancer invasion.

Main Methods:

• Lightsheet microscopy was used on intact tumors to visualize transitional junctions.
• A multimodal serial-section workflow integrating volumetric reconstruction and spatial transcriptomics was developed.
• Analysis included 319 spatial assays from 51 cancer cases.

Main Results:

• Loss of MGP and PLAT in breast cancer correlated with invasive transition and promoted tumorigenesis.
• Upregulation of GDF15, ALDH1A3, ANPEP, and FASN in prostate cancer was linked to invasive progression; knockdown suppressed proliferation and migration.
• Enrichment of specific tumor-associated macrophages (SPP1⁺, MS4A6A⁺) was observed in non-TNBC breast cancer transitions, suggesting immune involvement.

Conclusions:

• Novel gene-expression signatures and structural insights characterize the precancer to invasive transition in hormone-driven cancers.
• Specific molecular pathways (e.g., MGP, PLAT, GDF15) and immune cells (macrophages) are implicated as drivers of invasion.
• This research provides a foundation for understanding and potentially targeting cancer invasiveness.