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Next generation sequencing of parental RM cells and RM1 cells derived bone and lung metastases for preliminary assessment of differential tumor cell gene expression in bone

ABSTRACT: Using the immunocompetent bone-metastatic murine model of prostate cancer, the transcriptomes of proliferating (PKH26-) eCFP+/luc2+ RM1 cells (referred to as RM1536) were compared to FACS-isolated, proliferating (PKH26-) RM1536 cells derived from matched bone and lung metastases for preliminary assessment of gene alterations that may specifically occur in bone.

ORGANISM(S): Mus musculus

PROVIDER: GSE147099 | GEO | 2020/10/01

REPOSITORIES: GEO

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Project description:PurposeTo examine the usefulness of rich diffusion protocols with high b-values and varying diffusion time for probing microstructure in bone metastases. Analysis techniques including biophysical and mathematical models were compared with the clinical apparent diffusion coefficient (ADC).MethodsFour patients were scanned using 13 b-values up to 3,000 s/mm2 and diffusion times ranging 18-52 ms. Data were fitted to mono-exponential ADC, intravoxel incoherent motion (IVIM), Kurtosis and Vascular, extracellular, and restricted diffusion for cytometry in tumors (VERDICT) models. Parameters from the models were compared using correlation plots.ResultsADC and IVIM did not fit the data well, failing to capture the signal at high b-values. The Kurtosis model best explained the data in many voxels, but in voxels exhibiting a more time-dependent signal, the VERDICT model explained the data best. The ADC correlated significantly (p < 0.004) with the intracellular diffusion coefficient (r = 0.48), intracellular volume fraction (r = -0.21), and perfusion fraction (r = 0.46) parameters from VERDICT, suggesting that these factors all contribute to ADC contrast. The mean kurtosis correlated with the intracellular volume fraction parameter (r = 0.26) from VERDICT, consistent with the hypothesis that kurtosis relates to cellularity, but also correlated weakly with the intracellular diffusion coefficient (r = 0.18) and cell radius (r = 0.16) parameters, suggesting that it may be difficult to attribute physical meaning to kurtosis.ConclusionBoth Kurtosis and VERDICT explained the diffusion signal better than ADC and IVIM, primarily due to poor fitting at high b-values in the latter two models. The Kurtosis and VERDICT models captured information at high b using parameters (Kurtosis or intracellular volume fraction and radius) that do not have a simple relationship with ADC and that may provide additional microstructural information in bone metastases.

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Next generation sequencing of parental RM cells and RM1 cells derived bone and lung metastases for preliminary assessment of differential tumor cell gene expression in bone

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