Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech republic.
Neoplasma. 2012;59(2):191-201. doi: 10.4149/neo_2012_025.
Current diagnostic techniques are inefficient in distinguishing latent and low-risk forms of prostate cancer from high-risk forms. The present study is focused on determination of putative tumor markers of aggressive high-grade forms of prostate cancer. Potential markers were determined in blood sera of 133 patients (82 cases and 51 controls) and in cell lines (Gleason score 9-derived 22Rv1 and normal tissue derived PNT1A) on mRNA and protein levels. Alpha-methylacyl-CoA racemase (AMACR), metallothionein classes 1A and 2A (MT1A and MT2A) were determined and compared to prostate specific antigen (PSA) levels. On mRNA level, significantly increased expression of MT2A (2.4-fold), PSA (2.6-fold) and AMACR (8.4-fold) and insignificantly (1.9-fold) elevated MT1A in 22Rv1 compared to non-tumor PNT1A were determined. On protein level, significant enhancement of free PSA and total PSA in tumor cell line was evident. AMACR protein was 1.5-fold elevated in tumor line (below the level of significance). Contrary to mRNA, significantly (p = 0.01) reduced level of MT protein in tumor lines was determined. In the case of serum level, significantly enhanced MT level (4.5-fold) in patients' sera was found. No significant changes were observed in the case of AMACR. These findings indicate possible alternative role of MT to PSA prostate cancer marker. In addition, level of AMACR is distinctly higher in the Gleason score 9 in serum of patients and MT shows a descending trend in relation to Gleason score.
目前的诊断技术在区分潜伏性和低风险形式的前列腺癌与高风险形式方面效率低下。本研究集中于确定侵袭性高级别前列腺癌的推定肿瘤标志物。在 133 名患者（82 例和 51 例对照）的血清和细胞系（Gleason 评分 9 衍生的 22Rv1 和正常组织衍生的 PNT1A）上，在 mRNA 和蛋白水平上确定了潜在的标志物。测定了α-甲基酰基辅酶 A 消旋酶（AMACR）、金属硫蛋白 1A 和 2A（MT1A 和 MT2A），并与前列腺特异性抗原（PSA）水平进行了比较。在 mRNA 水平上，22Rv1 中 MT2A（2.4 倍）、PSA（2.6 倍）和 AMACR（8.4 倍）的表达显著增加，而 MT1A 则显著增加（1.9 倍）。在蛋白水平上，肿瘤细胞系中游离 PSA 和总 PSA 的显著增强是明显的。AMACR 蛋白在肿瘤系中升高 1.5 倍（低于显著性水平）。与 mRNA 相反，在肿瘤系中 MT 蛋白的水平显著降低（p=0.01）。在血清水平，在患者血清中发现 MT 水平显著增强（4.5 倍）。在 AMACR 方面没有观察到显著变化。这些发现表明 MT 可能替代 PSA 作为前列腺癌标志物。此外，在患者血清中，Gleason 评分 9 的 AMACR 水平明显升高，而 MT 水平与 Gleason 评分呈下降趋势。
