Polyploid cancer cells reveal signatures of chemotherapy resistance.
Michael J SchmidtAmin NaghdlooRishvanth K PrabakarMohamed KamalRadu CadaneanuIsla P GarrawayMichael LewisAna AparicioAmado Zurita-SaavedraPaul CornPeter KuhnKenneth J PientaSarah R AmendJames HicksPublished in: bioRxiv : the preprint server for biology (2024)
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 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 their expression of markers tied to cancer relapse, offering new potential avenues for therapeutic development.
Keyphrases
- circulating tumor cells
- single cell
- free survival
- prostate cancer
- circulating tumor
- copy number
- papillary thyroid
- gene expression
- rna seq
- bone marrow
- genome wide
- high throughput
- locally advanced
- squamous cell
- mitochondrial dna
- dna methylation
- case report
- binding protein
- healthcare
- newly diagnosed
- prognostic factors
- radiation therapy
- cardiovascular disease
- poor prognosis
- young adults
- mesenchymal stem cells
- type diabetes
- patient reported outcomes
- protein protein
- high glucose
- climate change
- lymph node metastasis
- benign prostatic hyperplasia
- big data
- human health
- stem cells
- breast cancer cells
- chronic kidney disease
- artificial intelligence
- peritoneal dialysis
- data analysis
- cell therapy
- low density lipoprotein