Abstract 450: Serum biomarkers in patients treated with stereotactic body radiation therapy (SBRT) for prostate cancer
Authors: Janowski Einsley , Suy Simeng , Varghese Rency S. , Timofeeva Olga , Field Stuart G. , Ostroff Rachel , Williams Steve , Dritschilo Anatoly , Collins Sean P. 
Published: July 2016

Purpose: The goal of this study was to determine the feasibility for developing prognostic protein biomarkers in serum samples from patients undergoing Stereotactic Body Radiation Therapy (SBRT) for organ confined prostate cancers.

Methods: 130 patients presenting with organ confined prostate cancers were treated with SBRT to doses of 35-36.25 Gy in 5 fractions. Peripheral blood samples were collected prospectively from patients at time 0 prior to radiation and serially after the first treatment (24 hours), follow-up months 1, 3, 6, 9, and 12 during the first year, and every 6 months thereafter, for up to 3 years. Processed study samples were analyzed by SomaLogic, Inc., using the SOMAscan Version 3 proteomic assay. Statistical analysis was performed on log-transformed data, with statistically significant differences identified by evaluating false discovery rate corrected p-values. Protein correlations were discovered with the Jonckheere-Terpstra (JT) test. Ingenuity Pathway Analysis (IPA) software was used to analyze cellular signaling pathways. PSA levels and clinical recurrence information were prospectively obtained at each follow-up visit and maintained in an institutional database.

Results:

Patient stratification by risk assessment identified 27 low-, 71 intermediate- and 32 high-risk patients in the study cohort. Proteins that function in cell proliferation, angiogenesis, protein signaling, gonad development, and cell migration correlated with Gleason's grade. CGA.LHB, KLK3, and CNTFR correlated both with tumor stage and Gleason's grade. With a median follow up of 3 years, ten patients experienced biochemical failures. While no proteins identified as differentially expressed in recurrent patients achieved significance, IPA pathway analysis of the top differentially expressed proteins converged on the IL-6 canonical pathway.

183 proteins were attributed to radiation effects on differential expression in patients by comparing pre-treatment to the 3 months post-treatment specimens. IPA network pathway analyses of these paired samples revealed changes in cell activation and signaling pathways, with the primary regulatory networks associated with ERK1/2, NF-κB, IFNG, ADIPOQ, histone 3, and histone 4. Of particular interest, high adiponectin levels in patients presenting with higher tumor stage decreased after radiation exposure, underscoring the potential for this molecule as a signal for determining response to radiation treatment.

Conclusion:

These hypothesis-generating experiments show differential serum protein levels in prostate cancer patient cohorts that have been stratified by risk factors and in longitudinal studies of patients following treatment with SBRT. Candidate biomarker proteins and molecular pathways have been identified for validation as potential predictors of prostate cancer response to radiation treatment.

Citation Format: Einsley Janowski, Simeng Suy, Rency S. Varghese, Olga Timofeeva, Stuart G. Field, Rachel Ostroff, Steve Williams, Anatoly Dritschilo, Sean P. Collins. Serum biomarkers in patients treated with stereotactic body radiation therapy (SBRT) for prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 450.