Polyploid cancer cells reveal signatures of chemotherapy resistance

Schmidt, Michael J, Naghdloo, Amin, Prabakar, Rishvanth K, Kamal, Mohamed, Cadaneanu, Radu, Garraway, Isla P, Lewis, Michael, Aparicio, Ana, Zurita-Saavedra, Amado, Corn, Paul, Kuhn, Peter, Pienta, Kenneth J, Amend, Sarah R, Hicks, James (November 2024) Polyploid cancer cells reveal signatures of chemotherapy resistance. Oncogene. ISSN 0950-9232 (Public Dataset)

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Abstract

Therapeutic resistance in cancer significantly contributes to mortality, with many patients eventually experiencing recurrence after initial treatment responses. Recent studies have identified therapy-resistant large polyploid cancer cells in patient tissues, particularly in late-stage prostate cancer, linking them to advanced disease and relapse. Here, we analyzed bone marrow aspirates from 44 advanced prostate cancer patients and found the presence of circulating tumor cells with increased genomic content (CTC-IGC) was significantly associated with poorer progression-free survival. Single cell copy number profiling of CTC-IGC displayed clonal origins with typical CTCs, suggesting complete polyploidization. Induced polyploid cancer cells from PC3 and MDA-MB-231 cell lines treated with docetaxel or cisplatin were examined through single cell DNA sequencing, RNA sequencing, and protein immunofluorescence. Novel RNA and protein markers, including HOMER1, TNFRSF9, and LRP1, were identified as linked to chemotherapy resistance. These markers were also present in a subset of patient CTCs and are associated with recurrence in public gene expression data. This study highlights the prognostic significance of large polyploid tumor cells, their role in chemotherapy resistance, and the expression of markers tied to cancer relapse, offering new potential avenues for therapeutic development.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders
diseases & disorders > cancer > drugs and therapies > chemotherapy
diseases & disorders > cancer > drugs and therapies
diseases & disorders > cancer > cancer types > prostate cancer
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Meyer Lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 22 November 2024
Date Deposited: 25 Nov 2024 13:49
Last Modified: 25 Nov 2024 13:49
Related URLs:
Dataset ID:
URI: https://repository.cshl.edu/id/eprint/41740

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