Spatial Mapping of the Precancer-to-Cancer Transition in Breast and Prostate
Breast and prostate cancers are both hormone-driven adenocarcinomas that undergo analogous invasion programs. Using lightsheet microscopy on intact tumors, we identified transitional junctions between precancerous and invasive regions. We then developed a multimodal serial-section workflow integrating volumetric reconstruction with spatial transcriptomics. Analysis of 319 spatial assays from 51 cases revealed gene-expression features and novel structural insights defining the shift from precancer to invasive disease. In breast cancer, loss of MGP and PLAT was associated with invasive transition and promoted tumorigenesis in functional assays. In prostate cancer, GDF15, ALDH1A3, ANPEP, and FASN were upregulated along invasive progression, and their knockdown in PC-3 cells suppressed proliferation and migration. Enrichment of tumor-associated macrophages (SPP1⁺, MS4A6A⁺) along non-TNBC breast cancer transitions highlights immune involvement as a potential driver of invasiveness.
Authors
- Xiangwei Fang (ORCID: https://orcid.org/0009-0004-8061-7680)
- Stephen T. Oh (ORCID: https://orcid.org/0000-0002-8564-5400)
- Preet Lal (ORCID: https://orcid.org/0009-0005-8258-3688)
- Y S Li
- Alla Y. Karpova (ORCID: https://orcid.org/0000-0001-5869-6336)
- Reyka G. Jayasinghe (ORCID: https://orcid.org/0000-0003-2368-4890)
- Sidharth V. Puram (ORCID: https://orcid.org/0000-0003-3543-889X)
- Cody Weimholt (ORCID: https://orcid.org/0000-0003-2926-343X)
- Benjamin J. Raphael (ORCID: https://orcid.org/0000-0003-1274-048X)
- Gary J. Patti (ORCID: https://orcid.org/0000-0002-3748-6193)
- Albert H. Kim (ORCID: https://orcid.org/0000-0002-1751-8493)
- Chia-Kuei Mo (ORCID: https://orcid.org/0009-0005-7056-0841)
- Andrew Houston (ORCID: https://orcid.org/0000-0001-5669-7335)
- Kooresh Isaac Shoghi (ORCID: https://orcid.org/0000-0003-3204-457X)
- Graham A. Colditz (ORCID: https://orcid.org/0000-0002-7307-0291)
- Michael C. Wendl (ORCID: https://orcid.org/0000-0002-5694-2668)
- Melissa A. Reimers (ORCID: https://orcid.org/0000-0002-5167-3630)
- Cynthia X. Ma (ORCID: https://orcid.org/0000-0002-8156-7492)
- Feng Chen (ORCID: https://orcid.org/0000-0002-2307-7954)
- Erik Storrs (ORCID: https://orcid.org/0000-0002-8041-0864)
- Peter O. Bayguinov (ORCID: https://orcid.org/0000-0002-5365-7490)
- John M. Herndon (ORCID: https://orcid.org/0000-0002-8378-9654)
- James A. J. Fitzpatrick (ORCID: https://orcid.org/0000-0002-7907-3602)
- Wen-hung Chou (ORCID: https://orcid.org/0000-0003-1941-3393)
- Rebecca Aft (ORCID: https://orcid.org/0000-0001-8569-7131)
- Foluso O. Ademuyiwa (ORCID: https://orcid.org/0000-0002-6766-2258)
- Robert S. Fulton (ORCID: https://orcid.org/0009-0006-6820-3404)
- William E. Gillanders (ORCID: https://orcid.org/0000-0002-0465-3071)
- Sherri R. Davies (ORCID: https://orcid.org/0000-0002-7141-8354)
- David Fenyö (ORCID: https://orcid.org/0000-0001-5049-3825)
- J Wang
- Hongyu Zheng (ORCID: https://orcid.org/0000-0002-7668-2090)
- Andrew Shinkle (ORCID: https://orcid.org/0000-0002-2369-9446)
- Milan G. Chheda (ORCID: https://orcid.org/0000-0001-8282-9098)
- Gaurav Bhatt
- Ryan C. Fields (ORCID: https://orcid.org/0000-0001-6176-8943)
- Russell K. Pachynski (ORCID: https://orcid.org/0000-0002-8966-7631)
- Bettina F. Drake (ORCID: https://orcid.org/0000-0001-9340-5848)
- Faria Anjum Simin
- Xiang Li (ORCID: https://orcid.org/0000-0003-1199-7152)
- Eric H. Kim (ORCID: https://orcid.org/0000-0002-0284-8342)
- Xiyi Wei (ORCID: https://orcid.org/0000-0002-0166-3194)
- Tao Ju (ORCID: https://orcid.org/0000-0002-1848-1012)
- Deborah J. Veis
- Li Ding (ORCID: https://orcid.org/0000-0003-1517-2975)
- John A. Olson (ORCID: https://orcid.org/0000-0002-7759-8317)
- R. Sherburne Figenshau (ORCID: https://orcid.org/0000-0003-0423-2792)
- Jennifer Ponce (ORCID: https://orcid.org/0009-0001-7648-6209)
- Michael Heinz (ORCID: https://orcid.org/0009-0006-8765-7073)
Institutions
- Memorial Sloan Kettering Cancer Center (US)
- University of Nevada, Reno (US)
- Princeton University (US)
- Washington University in St. Louis (US)
- Moffitt Cancer Center (US)
- NYU Langone Health (US)
- Washington University Medical Center (US)
Publication Details
- Journal
- Cancer Discovery
- Published
- 2026-04-17
- DOI
- https://doi.org/10.1158/2159-8290.cd-26-0012
- Primary Topic
- GDF15 and Related Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 0.00