Department of Pathology, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Department of Obstetrics and Gynecology, Otto von Guericke University Magdeburg, Gerhart-Hauptmann Str. 35, Magdeburg, Germany.
Pathol Res Pract. 2020 Dec;216(12):153257. doi: 10.1016/j.prp.2020.153257. Epub 2020 Oct 18.
Glyoxalase-1 (GLO-1) is the key enzyme in aldehyde defence in cancer cells. We here evaluated the prognostic impact and association with clinico-pathological parameters and relapse-free as well as overall survival in tumor samples from 187 breast cancer patients. The determined GLO1-immunoreactive score (GLO1-IRS) did not correlate with parameters such as grading, size, hormone receptors or ki67. However, an association of GLO1-IRS with the advanced glycation end product N(carboxymethyl)lysine (p = 0.07) and HER2 (p = 0.06), and a strong correlation with VEGF (p = 0.008) was found. In survival analysis, no significant impact of GLO-1 IRS could be deduced for all patients. However, GLO1-IRS correlated with treatment by radiotherapy (p = 0.008) and high GLO1-IRS predicted a shorter relapse free survival after radiotherapy (log-rank p = 0.067). METABRIC- and TCGA expression-data were analyzed for correlation of regulatory genes of the NF-κB-pathway (RELA, RELB, IRAK1), the oxidative-stress associated transcription factor nrf2 (NFE2L2), the receptor for AGEs (AGER, RAGE) as well as enzymes associated with aldehyde defense. Here, RELA, RELB and NFE2L2 correlated significantly with GLO1 expression, but there were conflicting results between the two data sources. In conclusion, GLO1 was highly expressed in cancer cells, correlated surprisingly weak with survival, but we could show a positive association with the AGE CML as well as VEGF. Gene expression data suggest a regulation of GLO-1 mRNA via both, inflammation (NF-kB) and oxidative stress (NFE2L2) in tumors.
甘油醛-3-磷酸脱氢酶 1（GLO-1）是癌细胞中醛防御的关键酶。我们在这里评估了 187 例乳腺癌患者肿瘤样本中预后的影响，并与临床病理参数以及无复发生存和总生存相关。确定的 GLO1-免疫反应评分（GLO1-IRS）与分级、大小、激素受体或 ki67 等参数无关。然而，GLO1-IRS 与晚期糖基化终产物 N（羧甲基）赖氨酸（p = 0.07）和 HER2（p = 0.06）呈正相关，与 VEGF 呈强相关（p = 0.008）。在生存分析中，不能从所有患者中推断出 GLO-1 IRS 的显著影响。然而，GLO1-IRS 与放疗（p = 0.008）相关，高 GLO1-IRS 预测放疗后无复发生存期较短（对数秩 p = 0.067）。分析了 METABRIC 和 TCGA 表达数据，以确定 NF-κB 途径的调节基因（RELA、RELB、IRAK1）、与氧化应激相关的转录因子 nrf2（NFE2L2）、AGEs 的受体（AGER、RAGE）以及与醛防御相关的酶的相关性。在这里，RELA、RELB 和 NFE2L2 与 GLO1 表达显著相关，但这两个数据源之间存在相互矛盾的结果。总之，GLO1 在癌细胞中高表达，与生存的相关性较弱，但我们发现它与 AGE CML 以及 VEGF 呈正相关。基因表达数据表明，在肿瘤中 GLO-1 mRNA 的表达通过炎症（NF-κB）和氧化应激（NFE2L2）进行调节。
