Circulating tumor cells as predictive biomarkers in the risk stratification of DCIS: Evidence of early dissemination
Overtreatment of patients with ductal carcinoma in situ (DCIS) is driven by a lack of a reliable prognostic biomarker. Widespread mammographic screening has resulted in a substantial increase in women diagnosed with DCIS. To improve patient risk stratification, we investigate circulating tumor cells (CTCs) as a biomarker for DCIS patients' biological aggressiveness and as an indicator of early dissemination. We apply microfluidics to enrich CTCs from 34 patients with DCIS and find a significantly higher concentration of CTCs compared to in healthy controls. We profile CTCs and matched DCIS tissues using single-cell RNA sequencing. We find that CTCs express higher clonal aberrations when compared to white blood cells from the same samples, and clonal comparisons between matched tissue and CTC samples provide evidence for an evolutionary bottleneck model. mRNA expression in CTC reveals EMT/MET and immunoregulatory pathway regulation with a suggestion of racial differences. Last, we provide support for early dissemination in DCIS using a Mouse IntraDuctal model.
Authors
- Sunitha Nagrath (ORCID: https://orcid.org/0000-0002-1497-7977)
- Ashley Huppe (ORCID: https://orcid.org/0000-0002-5571-5682)
- Fariba Behbod (ORCID: https://orcid.org/0000-0001-6281-2651)
- Camron Smith (ORCID: https://orcid.org/0009-0009-0245-2047)
- Andrew K. Godwin (ORCID: https://orcid.org/0000-0002-3987-9580)
- Christa Balanoff (ORCID: https://orcid.org/0000-0002-4320-122X)
- Jamie Wagner (ORCID: https://orcid.org/0000-0002-3710-7798)
- Neha Nagpal
- Kelsey E. Larson (ORCID: https://orcid.org/0000-0003-1977-9459)
- Brittany Rupp (ORCID: https://orcid.org/0000-0003-3654-9882)
- Allison M. Aripoli (ORCID: https://orcid.org/0000-0002-7379-6025)
- Carol J. Fabian (ORCID: https://orcid.org/0000-0002-8855-4133)
- Max S. Wicha (ORCID: https://orcid.org/0000-0003-4180-7727)
- Jessica Peterson
- Onalisa Winblad (ORCID: https://orcid.org/0000-0003-3560-2813)
- Yan Hong
- Timothy A. Fields (ORCID: https://orcid.org/0000-0003-0665-370X)
- Molly Hill
Institutions
- Virginia Commonwealth University (US)
- University of Michigan (US)
- University of Kansas Medical Center (US)
- BioSurfaces (United States) (US)
Publication Details
- Journal
- Science Advances
- Published
- 2025-10-29
- DOI
- https://doi.org/10.1126/sciadv.adz0187
- Primary Topic
- Cancer Cells and Metastasis
- Type
- article
- Field-Weighted Citation Impact
- 0.00