Abstract 1971: Leveraging CK and CD45 dual positive cells as cancer diagnostic markers in liquid biopsy

Liquid biopsy has emerged as a revolutionary, non-invasive diagnostic tool, enabling real-time monitoring of tumor dynamics. Circulating tumor cells (CTCs), shed from primary or metastatic tumors into the bloodstream, represent a critical component of liquid biopsy with immense potential for early cancer detection, prognosis, and therapeutic monitoring [1]. While identification of CTCs as cytokeratin (CK) positive and CD45 negative is standard of immunofluorescence assay among cells in blood sample, curious cases have been reported that the presence of CK and CD45 dual positive (DP) cells [2]. However, neither the identity of DP cells nor the roles of them had been understood. Rather, their presences were neglected so far. This presentation highlights recent findings of the DP cells about their identity and their potential roles as biomarkers, especially cancer diagnostic markers. Our state-of-the-art technologies [3] enabled detection and isolation of the DP cells, streamlined to single cell RNA-seq and the downstream analysis with high quality of data in spite of heterogeneity. Our studies focus on the molecular profiling of CTCs and DP cells to identify transcriptional signatures that correlate with tumor metastasis mechanisms. Additionally, emerging evidence underscores the potential edges of the prognostic value of DP cell enumeration over CTCs. By bridging the gap between liquid biopsy innovations and clinical application, DP-cell-based diagnostics hold promise for transforming precision oncology. Future directions include integrating DP analysis with other biomarkers, such as CTC, circulating tumor DNA and extracellular vesicles, to construct a comprehensive liquid biopsy platform. This work emphasizes the role of DP cells as a novel target of liquid biopsy, paving the way for earlier interventions and more personalized therapeutic strategies in cancer care. References: [1] Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW and Hayes DF: Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 351:781-791. 2004. [2] Carolina Reduzzi, Marta Vismara, Lorenzo Gerratana, Marco Silvestri, Filippo De Braud, Francesco Raspagliesi, Elena Verzoni, Serena Di Cosimo, Laura D. Locati, Massimo Cristofanilli, Maria Grazia Daidone, Vera Cappelletti, The curious phenomenon of dual-positive circulating cells: Longtime overlooked tumor cells, Seminars in Cancer Biology, Volume 60, 2020, [3] Lee, A.C., Lee, Y., Choi, A. et al. Spatial epitranscriptomics reveals A-to-I editome specific to cancer stem cell microniches. Nat Commun 13, 2540 (2022). Citation Format: Amos Chungwon Lee, Wooseok Lee, Sumin Lee, Han-Byoel Lee, Sunghoon Kwon. Leveraging CK and CD45 dual positive cells as cancer diagnostic markers in liquid biopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1971.