CyTOF-based profiling of circulating tumor cells predicts aggressiveness and therapy response in SCLC liquid biopsies at a personalized level
Small-cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma characterized by high numbers of circulating tumor cells (CTCs). We applied CyTOF and a 20-marker antibody panel to detect and phenotype CTCs directly in liquid biopsies of 51 SCLC patients (treatment-naïve, chemotherapy and immunotherapy-treated, and tarlatamab-treated), of which a subset were longitudinally tracked. Unsupervised clustering revealed distinct cell populations enriched in patient liquid biopsies compared to those from healthy donors. Further analysis identified CTC populations of the three established SCLC subtypes driven by the high expression of ASCL1, NeuroD1, and POU2F3 transcription factors respectively. Significant differences in CTC EMT markers, established therapeutic targets (e.g. DLL3), and subtype heterogeneity were observed between naïve versus treated samples. Changes in subtype proportions were observed in longitudinally tracked samples in both treatment modalities. Our study demonstrates the utility of CyTOF for high-resolution CTC profiling, offering dynamic insights into CTC heterogeneity, treatment response, and resistance mechanisms.
Authors
- Shafqat Ehsan (ORCID: https://orcid.org/0000-0002-0561-690X)
- Alberto José da Silva Duarte (ORCID: https://orcid.org/0000-0002-8707-4904)
- Catherine M. Ruoff (ORCID: https://orcid.org/0000-0003-0072-3586)
- Thomas Welte (ORCID: https://orcid.org/0000-0002-1749-9886)
- Bingnan Zhang (ORCID: https://orcid.org/0000-0002-1821-6243)
- C. Allison Stewart (ORCID: https://orcid.org/0000-0002-7758-1179)
- Benedict Anchang (ORCID: https://orcid.org/0000-0002-5576-5647)
- Loukia Georgiou Karacosta (ORCID: https://orcid.org/0000-0002-1491-4773)
- Alejandra G. Serrano (ORCID: https://orcid.org/0000-0001-6759-9239)
- Mukulika Bose (ORCID: https://orcid.org/0000-0002-2347-7413)
- Carl M. Gay (ORCID: https://orcid.org/0000-0002-4907-0718)
- Sayantan Bhattacharyya (ORCID: https://orcid.org/0000-0003-1960-4309)
- Robert J. Cardnell (ORCID: https://orcid.org/0009-0005-6203-0234)
- Fabiola Ester Lujan (ORCID: https://orcid.org/0000-0002-3719-3585)
- Luisa M. Solis Soto (ORCID: https://orcid.org/0000-0002-1253-630X)
- Lixia Diao (ORCID: https://orcid.org/0000-0001-6995-4492)
- Ashley Victorian
- Jiaqi Li (ORCID: https://orcid.org/0000-0001-9038-9010)
- Jing Wang (ORCID: https://orcid.org/0000-0001-9413-2378)
- Ken Chen (ORCID: https://orcid.org/0000-0003-4013-5279)
- Runsheng Wang (ORCID: https://orcid.org/0000-0002-8016-5934)
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- National Institute of Environmental Health Sciences (US)
- National Cancer Institute (MY)
- Scripps MD Anderson Cancer Center (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2025-12-19
- DOI
- https://doi.org/10.64898/2025.12.16.694669
- Citations
- 1
- Primary Topic
- Lung Cancer Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 1.05
Funders
- U.S. Department of Defense
- Cancer Prevention and Research Institute of Texas
- National Institutes of Health
- University of Texas MD Anderson Cancer Center
- National Cancer Institute
- Moonshot Research and Development Program
- Cancer Moonshot