Abstract B071: Circulating tumor cells as liquid biopsies of skeletal metastases from prostate cancer

Autor: Daniel Åhs, Helena Brisby, Karin Larsson, Jan-Erik Damber, Andreas Josefsson, Karin Welén
Rok vydání: 2018
Předmět:
Zdroj: Cancer Research. 78:B071-B071
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.prca2017-b071
Popis: Background: Circulating tumor cells (CTC) are promising biomarkers in advanced prostate cancer. Since they are seeded from metastases, they may also serve as liquid biopsies for skeletal metastases that are difficult to sample. The aim of the present study was to evaluate to which extent CTCs reflect the phenotype of skeletal metastases, and thereby their potential to serve as a clinical tool in individualizing treatment of metastatic prostate cancer. Materials and Method: CTC and tissue from skeletal metastases were sampled from 22 patients (8 GnRH-naïve and 14 castration-resistant) during surgery for spinal cord compression symptoms. CTCs were sampled prior to removal of metastatic tissue, and isolated with AdnaTest ProstateCancerSelect/Detect (Qiagen). Resulting cDNA was preamplified in a multiplex reaction and analyzed for expression of 37 genes related to prostate cancer progression and metastasis with qPCR. RNA was extracted from the metastatic tissue with RNeasy Plus Universal Mini kit (Qiagen), and gene expression was assessed in the same way as for CTCs. EPCAM expression level was used as internal control to enable normalization to epithelial content (CTCs or tumor tissue) of the samples. Correlation of detected signals between matched CTC and tissue was calculated with Pearson correlations. Results: 12 of the 37 genes displayed expression patterns that were correlating in paired CTC and metastatic samples. Using this subset of genes, the metastases could be grouped similarly to when all 37 genes were included in hierarchical clustering analyses. Using a smaller subset of genes and patients, defined by gene detection frequency in CTC samples, hierarchical clustering of gene expression in CTCs could group the patients similar to when expression data from the metastases were used. In addition, a subset of genes discriminating GnRH-naïve from castration-resistant metastases could be analyzed in CTCs, where it, to a large extent, could identify the same groups of patients. Conclusion: This study shows that gene expression patterns in CTCs can reflect those of metastases. However, careful selection of the genes to include is important. In addition, insufficient detection sensitivity in CTC analyses limits the range of the genes to be analyzed with current methodology. Taken together, the results imply that CTC phenotyping is a promising tool for individualized therapy in metastatic prostate cancer. Citation Format: Andreas Josefsson, Karin Larsson, Daniel Åhs, Helena Brisby, Jan-Erik Damber, Karin Welén. Circulating tumor cells as liquid biopsies of skeletal metastases from prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B071.
Databáze: OpenAIRE