Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
PLoS One. 2013 Sep 10;8(9):e74014. doi: 10.1371/journal.pone.0074014. eCollection 2013.
Glyoxalase 1 is a scavenging enzyme of potent precursors in reactive oxygen species formation and is involved in the occurrence and progression of human malignancies. Glyoxalase I A111E polymorphism has been suggested to influence its enzymatic activity. The present study was aimed at investigating the association of this polymorphism with oxidative stress and its implications in prostate cancer progression or survival. The polymorphism was genotyped in human differently aggressive and invasive prostate cancer cell lines, in 571 prostate cancer or 588 benign prostatic hyperplasia patients, and 580 healthy subjects by Polymerase Chain Reaction/Restriction Fragment Length Polymorphism. Glyoxalase 1 activity, the pro-oxidant Glyoxalase 1-related Argpyrimidine and oxidative stress biomarkers were evaluated by biochemical analyses. Glyoxalase 1 polymorphism was associated with an increase in Glyoxalase 1-related pro-oxidant Argpyrimidine and oxidative stress levels and cancer progression. The mutant A allele conferred a modest risk of prostate cancer, a marked risk of prostate cancer progression and a lower survival time, compared to the wild C allele. The results of our exploratory study point out a significant role for Glyoxalase 1 in prostate cancer progression, providing an additional candidate for risk assessment in prostate cancer patients and an independent prognostic factor for survival. Finally, we provided evidence of the biological plausibility of Glyoxalase 1 polymorphism, either alone or in combination with other ones, all related to oxidative stress control that represents a key event in PCa development and progression.
一氧酰基酶 1 是活性氧形成中有效前体的清除酶，参与人类恶性肿瘤的发生和发展。一氧酰基酶 I A111E 多态性被认为影响其酶活性。本研究旨在探讨该多态性与氧化应激的关系及其对前列腺癌进展或生存的影响。通过聚合酶链反应/限制性片段长度多态性，在不同侵袭性和侵袭性的前列腺癌细胞系、571 例前列腺癌或 588 例良性前列腺增生患者和 580 例健康受试者中对该多态性进行了基因分型。通过生化分析评估一氧酰基酶 1 活性、促氧化剂一氧酰基酶 1 相关的精氨酸嘧啶和氧化应激生物标志物。一氧酰基酶 1 多态性与一氧酰基酶 1 相关促氧化剂精氨酸嘧啶和氧化应激水平的升高以及癌症进展相关。与野生型 C 等位基因相比，突变 A 等位基因赋予前列腺癌、前列腺癌进展和生存时间降低的适度风险。我们的探索性研究结果表明，一氧酰基酶 1 在前列腺癌进展中具有重要作用，为前列腺癌患者的风险评估提供了另一个候选标志物，并为生存提供了一个独立的预后因素。最后，我们提供了一氧酰基酶 1 多态性的生物学合理性证据，无论是单独存在还是与其他与氧化应激控制相关的多态性，氧化应激控制是前列腺癌发展和进展的关键事件。
