EPCA AND EPCA-2 AS POTENTIAL BIOMARKERS FOR PROSTATE CANCER DETECTION
Authors:
E. S. Leman; R. H. Getzenberg
Published in:
Urol List 2007; 5(4): 6-9
Overview
Despite this remarkable success, there have been limitations attributed to the use of prostate specific antigen (PSA) as a means for prostate cancer screening and detection. PSA is not specific for prostate cancer and as such is often found elevated in other conditions associated with the aging male such as benign prostatic hyperplasia (BPH), as well as men with prostatitis. The magnitude of this problem is large in that there are more than twenty-five million men which have had at least one negative biopsy due to an elevated PSA level. In many of these individuals, they are not certain if the cancer was missed upon the biopsy or whether they actually do not have prostate cancer. A more specific tool that could identify which individuals actually have prostate cancer and differentiate them from those without the disease would be of tremendous value.
Utilizing a focused proteomic approach, our laboratory has identified novel prostate cancer associated biomarkers. One of the hallmarks of the cancer cell is alterations in the shape, size, and morphometry of the nucleus. Since nuclear changes are one of the key features the pathologist uses to identify cancer cells, our goal was to find something at the molecular level that would equal what the pathologist was seeing under the microscope. We therefore focused our effort on the nuclear structural elements termed the nuclear matrix. In doing so, we identified two prostate cancer biomarkers that are associated with the nuclear structure: Early Prostate Cancer Antigen (EPCA) and Early Prostate Cancer Antigen 2 (EPCA-2). These are distinct proteins with the only similarity being the technique that was used to identify them. While EPCA has been shown to be a potentially useful tissue based marker for prostate cancer, EPCA-2 is a serum marker of the disease. In this review, we discuss the role of nuclear structural proteins as potential biomarkers of prostate cancer.
Key words:
nuclear structural elements, nuclear matrix, prostate cancer, biomarkers, EPCA, EPCA-2
Sources
1. Jemal A, Siegel R, Ward E et al. Cancer statistics, 2007. CA Cancer J Clin 2007; 57(1): 43-66.
2. Nickerson JA. Nuclear dreams: the malignant alteration of nuclear architecture. J Cell Biochem 1998; 70(2): 172-180.
3. Getzenberg RH, Pienta KJ, Huang EY, Coffey DS. Identification of nuclear matrix proteins in the cancer and normal rat prostate. Cancer Res 1991; 51(24): 6514-6520.
4. Leman ES, Arlotti JA, Dhir R et al. Characterization of the nuclear matrix proteins in a transgenic mouse model for prostate cancer. J Cell Biochem 2002; 86(2): 203-212.
5. Lakshmanan Y, Subong EN, Partin AW. Differential nuclear matrix protein expression in prostate cancers: correlation with pathologic stage. J Urol 1998; 159(4): 1354-1358.
6. Partin AW, Getzenberg RH, CarMichael MJ et al. Nuclear matrix protein patterns in human benign prostatic hyperplasia and prostate cancer. Cancer Res 1993; 53(4): 744-746.
7. Pienta KJ, Lehr JE. A common set of nuclear matrix proteins in prostate cancer cells. Prostate 1993; 23(1): 61-67.
8. Getzenberg RH. Nuclear matrix and the regulation of gene expression: tissue specificity. J Cell Biochem 1994; 55(1): 22-31.
9. Durfee T, Mancini MA, Jones D et al. The amino-terminal region of the retinoblastoma gene product binds a novel nuclear matrix protein that co-localizes to centers for RNA processing. J Cell Biol 1994; 127(3): 609-622.
10. Staufenbiel M, Deppert W. Different structural systems of the nucleus are targets for SV40 large T antigen. Cell 1983; 33(1): 173-181.
11. Miller TE, Beausang LA, Winchell LF, Lidgard GP. Detection of nuclear matrix proteins in serum from cancer patients. Cancer Res 1992; 52(2): 422-427.
12. Partin AW, Yoo J, Carter HB et al. The use of prostate specific antigen, clinical stage and Gleason score to predict pathological stage in men with localized prostate cancer. J Urol 1993; 150(1): 110-114.
13. Dhir R, Vietmeier B, Arlotti J et al. Early identification of individuals with prostate cancer in negative biopsies. J Urol 2004; 171(4): 1419-1423.
14. Uetsuki H, Tsunemori H, Taoka R et al. Expression of a novel biomarker, EPCA, in adenocarcinomas and precancerous lesions in the prostate. J Urol 2005; 174(2): 514-518.
15. Paul B, Dhir R, Landsittel D et al. Detection of prostate cancer with a blood-based assay for early prostate cancer antigen. Cancer Res 2005; 65(10): 4097-4100.
16. Leman ES, Cannon GW, Trock BJ et al. EPCA-2: a highly specific serum marker for prostate cancer. Urology 2007; 69(4): 714-720.
17. Leman ES, Cannon GW, Trock BJ et al. Further analysis of serum based EPCA-2 as a specific prostate cancer associated biomarker. In: The American Urological Association May 19-24, 2007: Anaheim: CA.
18. Cooner WH, Mosley BR, Rutherford CL Jr et al. Prostate cancer detection in a clinical urological practice by ultrasonography, digital rectal examination and prostate specific antigen. J Urol 1990; 143(6): 1146- 1152; discussion 52-54.
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Paediatric urologist UrologyArticle was published in
Urological Journal
2007 Issue 4
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