In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 711-711
Abstract:
Prostate cancer (PCa) is the second most frequently diagnosed form of male cancer and shares similar symptoms with BPH (Benign Prostate Hyperplasia), a disease characterized by prostate enlargement. Elevated levels of prostate-specific antigen (PSA) can be observed with either benign or malignant growth of the prostate and therefore cannot effectively discriminate between these two prostate diseases. Currently, a test that sensitively and accurately distinguishes between BPH and localized prostate cancer does not exist creating an urgent need for novel biomarkers that can successfully distinguish between these two prostate diseases. The goal of this study was to identify and validate non-invasive urinary biomarkers that distinguish between BPH and PCa. Our previous proteomic study identified elevated levels of several proteins, including EGF (epidermal growth factor), HE-4 (human epididymis protein 4), COL1A1 (collagen, type I, alpha 1) and other proteins in the urine of PCa patients compared to urine samples from patients with BPH. In this current study we have analyzed and validated the presence of EGF, HE-4 and COL1A1 by enzyme-linked immunosorbent assay (ELISA). Our ELISA experiments revealed that COL1A1 was significantly (P & lt; 0.002) elevated in the urine of patients diagnosed with early or localized PCa vs. BPH. In vitro experiments performed on seven different prostate cell lines identified cells from the tumor microenvironment that secrete the highest levels of COL1A1. Expression of COL1A1 by these cells was confirmed by immunohistochemistry (IHC) using prostate tissue microarrays (TMA). In addition, protein array experiments identified elevated levels of several proteases in the urine of PCa patients, including MMP-9, uPA, ADAM-TS1 and several cathepsins. Substrate gel electrophoresis (zymography) revealed elevated activity of both MMP-9 and MMP-2 in urine from PCa patients. These data suggest that MMP-9 and MMP-2 may participate in the cleavage of collagen type 1, resulting in elevated levels of COL1A1 in urine of PCa patients. We are currently testing this hypothesis. In summary, COL1A1 may represent a novel non-invasive urinary biomarker that can effectively discriminate between BPH vs. localized PCa. (Supported by The Ellison Foundation) Citation Format: Andrej Jedinak, Camille Vuichoud, Andrew El-Hayek, Katherine Kaplan, Jason Savage, Sarah Prophet, Adam S. Feldman, Kevin A. Camphausen, Kevin R. Loughlin, Marsha A. Moses. Mechanistic implications of COL1A1 as a prostate cancer biomarker [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 711. doi:10.1158/1538-7445.AM2017-711
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-711
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
