Abstract

Abstract The purpose of this study is to investigate the correlation of neuropilin-2 (NRP2) and its ligand, vascular endothelial growth factor-C (VEGF-C), with treatment outcomes and resistance in prostate cancer patients. 166 prostate cancer patient serum samples were obtained from the Integrated Cancer Repository for Cancer Research at the University of Nebraska Medical Center. 11 patients were excluded for having a non-prostate genitourinary cancer or more than one concurrent cancer. Patients were categorized as untreated, primary treatment, remission, and secondary treatment based on when their serum sample was collected. Primary treatment indicated current treatment with first-line medical therapy, remission indicated those without evidence of disease after prostatectomy or first-line medical therapy, and secondary therapy indicated second-line treatment currently being given due to treatment-resistant disease. Other variables collected include age, race, ethnicity, prostate-specific antigen (PSA) measured at the time of diagnosis, PSA measured at the time of serum sample collection, Gleason score, and clinical stage using the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) system. Finally, VEGF-C levels in patient serum were measured using a commercially available ELISA assay (R&D System, Minneapolis, MN). The final data was analyzed using a linear regression model to compare VEGF-C levels between treatment groups, as well as VEGF-C level correlation with each of the other variables collected. Results: All patients were male with an age range of 47 to 85 years, with a mean age of 65.3 years. Most were white (n=135) and non-Hispanic (n=148). VEGF-C levels ranged from 341 pg/ml to 15,983 pg/ml, with a mean of 3,787 pg/ml. Of the 155 patients, 8 were untreated, 26 were in primary therapy, 66 were in remission, and 52 were in secondary therapy. Results showed no statistically significant correlation between VEGF-C levels and PSA at diagnosis, PSA at serum collection, Gleason score, or clinical stage. The most interesting difference between treatment groups was a higher VEGF-C level in remission (mean 63.48 pg/ml) versus secondary therapy (mean 55.31 pg/ml), although this was not statistically significant (p=0.089). Conclusions: Our results indicated that plasma VEGF-C alone is not a prognostic indicator for prostate cancer. Since our studies using cell culture and animal models of prostate cancer have indicated the role of VEGF-C and the NRP2 axis in promoting metastasis and therapy resistance in prostate cancer, it would be useful to determine both the VEGF-C and NRP2 levels in the plasma of the same patients and study whether their level together would predict the outcome of medical therapy. Our ongoing experiments to determine plasma NRP2 levels in this patient cohort should be able to test this hypothesis. Citation Format: Sarah A. Mullen, Dipanwita Das, Samikshan Dutta, Robin R. High, Lynette M. Smith, Benjamin A. Teply, Kaustubh Datta. Identifying a surrogate biomarker for neuropilin-2 axis in serum of prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2168.

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