In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 7_suppl ( 2015-03-01), p. 166-166
Abstract:
166 Background: Prostate cancer is a heterogeneous disease with differences in tumor stromal interactions contributing to variability in treatment response and outcome. Gene expression of peripheral blood cells is altered by interactions with neoplastic tissue. We previously developed a peripheral whole blood six-gene signature prognostic for survival in mCRPC. Here we evaluate how different clinical disease states and treatment with different therapeutic agents impact this signature. Methods: Whole blood was collected in PAXgene Blood RNA tubes in two cohorts of prostate cancer patients, one at Mount Sinai (n=135), the other in Munich (n=59), in the context of prospective clinical studies. Whole blood RNA was extracted and the six target genes were amplified using qPCR. Scores were derived using normalized cycle threshold (ΔCT) values of the six genes, according to the model: 2 x ABL2 + SEMA4D + ITGAL – C1QA – TIMP1 – CDKN1A. Patients were categorized by disease state in the Mount Sinai cohort, and by treatment received in the Munich cohort, for data analysis. Results: CRPC is the only disease state with a mean six-gene score (18.06) above the high-risk cutoff (17.9), and is significantly higher than localized or hormone sensitive advanced disease (16.07, 16.52, respectively; p=0.0002). Among patients with localized disease, there was no significant difference in the mean six-gene scores for patients with low-, intermediate-, and high-risk disease (16.07, 15.33, 16.66, respectively; p=0.27). In CRPC patients treated with docetaxel, there are significant changes to the six-gene score over the course of treatment (p=0.002), with a notable percentage decrease (-6.2%) at the 2-8 week timepoint that is not observed in patients treated with abiraterone or enzalutamide. Conclusions: Gene expression profiling of whole blood is influenced by the clinical state of prostate cancer as seen by differences to the six-gene score from localized to castrate resistant disease. Cytotoxic chemotherapy appears to modulate the six-gene score, something not seen with AR-directed therapies. Further investigation will be needed to understand the significance of these changes.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2015.33.7_suppl.166
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2015
detail.hit.zdb_id:
2005181-5
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