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  candidate PCa CTC CRPC

Overall DesignA total of 221 single candidate prostate CTCs were isolated from 18 patients with metastatic prostate cancer and 4 patients with localized prostate cancer. Of these, 133 cells (60%) had RNA of sufficient quality for amplification and next generation RNA sequencing, and 122 (55%) had >100,000 uniquely aligned sequencing reads. In addition to candidate CTCs, we also obtained comprehensive transcriptomes for 12 bulk primary prostate cancers (macrodissected for >70% tumor content), 30 single cells derived from four different prostate cancer cell lines, and 5 patient-derived leukocyte controls. The leukocytes were readily distinguished by their expression of hematopoietic lineage markers and served to exclude any CTCs with potentially contaminating signals. Strict expression thresholds were used to define lineage-confirmed CTCs, scored by prostate lineage-specific genes (PSA, PSMA, AMACR, AR) and standard epithelial markers (KRT7, KRT8, KRT18, KRT19, EpCAM). 28 cells were excluded given the presence of leukocyte transcripts suggestive of cellular contamination or misidentification during selection, and 17 cells were excluded given low expression of both prostate lineage-specific genes and 5 standard epithelial markers. The remaining 77 cells, defined as lineage-confirmed CTCs, displayed expression of either prostate lineage-specific or epithelial genes, and low expression of leukocyte-specific genes, consistent with their tumor of origin.
SummaryProstate cancer is initially responsive to androgen deprivation, but the effectiveness of androgen receptor (AR) inhibitors in recurrent disease is variable. Biopsy of bone metastases is challenging, hence sampling circulating tumor cells (CTCs) may reveal drug resistance mechanisms. We established single cell RNA-sequencing profiles of 77 intact CTCs isolated from 13 patients (mean 6 CTCs/patient) using microfluidic enrichment. Single CTCs from each individual display considerable heterogeneity, including expression of AR gene mutations and splicing variants. Retrospective analysis of CTCs from patients progressing on AR inhibitor, compared with untreated cases indicates activation of noncanonical Wnt signaling (P=0.0064). Ectopic expression of Wnt5a in prostate cancer cells attenuates the antiproliferative effect of AR inhibition, while its suppression in drug-resistant cells restores partial sensitivity, a correlation also evident in an established mouse model. Thus, single cell analysis of prostate CTCs reveals heterogeneity in signaling pathways that could contribute to treatment failure.
Dataset viewGSE67980

Samples in candidate PCa CTC CRPC

Displaying 21-30 of 33 results.
SeriesSampleInstrumentOrganismTitleCell Source
GSE67980GSM1660093AB 5500xl Genetic AnalyzerHomo sapiensPr18.1.9candidate PCa CTC CRPC
GSE67980GSM1660094AB 5500xl Genetic AnalyzerHomo sapiensPr18.2.4candidate PCa CTC CRPC
GSE67980GSM1660095AB 5500xl Genetic AnalyzerHomo sapiensPr20.1.2candidate PCa CTC CRPC
GSE67980GSM1660096AB 5500xl Genetic AnalyzerHomo sapiensPr22.1.1candidate PCa CTC CRPC
GSE67980GSM1660097AB 5500xl Genetic AnalyzerHomo sapiensPr22.1.3candidate PCa CTC CRPC
GSE67980GSM1660098AB 5500xl Genetic AnalyzerHomo sapiensPr9.1.5candidate PCa CTC CRPC
GSE67980GSM1660099AB 5500xl Genetic AnalyzerHomo sapiensPr9.1.7candidate PCa CTC CRPC
GSE67980GSM1660100AB 5500xl Genetic AnalyzerHomo sapiensPr9.2.1candidate PCa CTC CRPC
GSE67980GSM1660101AB 5500xl Genetic AnalyzerHomo sapiensPr9.2.2candidate PCa CTC CRPC
GSE67980GSM1660102AB 5500xl Genetic AnalyzerHomo sapiensPr9.3.2candidate PCa CTC CRPC

Gene rank in candidate PCa CTC CRPC

Displaying 31-40 of 18557 results.
Rank orderGene SymbolEnsembl ID