谷胱甘肽 S-转移酶 P1 多态性与肝癌患者氧化应激的关系。

Relation between GSTP1 polymorphism and oxidative stress in patients with hepatocellular carcinoma.

机构信息

The Department of Clinical Pathology, Elkhanka Central Hospital, Qualiobeya, Egypt.

The Department of Clinical and Chemical Pathology, NCI, Cairo, Egypt.

出版信息

J Egypt Natl Canc Inst. 2020 Oct 2;32(1):38. doi: 10.1186/s43046-020-00049-x.

DOI:10.1186/s43046-020-00049-x

PMID:33006026

Abstract

BACKGROUND

Glutathione can reduce the oxidative stress by converting the unstable to stable molecules and its status in hepatocellular carcinoma (HCC) is correlated with tumor growth and metastasis. Glutathione S-transferase Pi (GSTP1) is reported to detoxify the xenobiotic substrates by catalyzing their conjugation to reduced glutathione (GSH) and its over-expression was demonstrated in the early stages of HCC, while loss of GSTP1 has been suggested to increase the risk of deoxyribonucleic acid (DNA) damage and mutation. The aim of this study is to assess the relationship of GSTP1 polymorphism Ile105Val (rs1695 A > G) with HCC risk, and to investigate the oxidative stress status of HCC patients by measuring the antioxidant glutathione (GSH) levels. This study was conducted on 99 newly diagnosed HCC patients and 80 apparently healthy individuals as a normal control group. All participants were subjected to the measurement of plasma GSH levels according to Ellman's method, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the detection of GSTP1 polymorphismIle105Val (rs1695 A > G).

RESULTS

The occurrence of either the mutant homozygous or the mutant heterozygous genotype of GSTP1 was significantly higher in HCC patients, while the occurrence of the wild genotype was significantly higher among the normal control subjects. Mutant GSTP1 genotype, older age, male gender, and high serum alanine aminotransferase (ALT) were associated with increased risk of development of HCC. The best sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value), and overall diagnostic performance for plasma GSH at a cutoff level of 2003.5 μM/mg were 57.6%, 52.5%, 60%, and 40%. The area under the curve for GSH was 0.562.

CONCLUSION

Mutant GSTP1 genotype was an independent prognostic factor for increased HCC risk which can be used in a risk assessment model for HCC. Plasma GSH presents insufficient sensitivity and specificity for HCC.

摘要

背景

谷胱甘肽可以通过将不稳定的分子转化为稳定的分子来减少氧化应激，其在肝细胞癌（HCC）中的状态与肿瘤生长和转移有关。谷胱甘肽 S-转移酶 Pi（GSTP1）被报道通过催化其与还原型谷胱甘肽（GSH）的共轭反应来解毒异生物质底物，其在 HCC 的早期阶段表达增加，而 GSTP1 的缺失被认为会增加脱氧核糖核酸（DNA）损伤和突变的风险。本研究旨在评估 GSTP1 多态性 Ile105Val（rs1695 A > G）与 HCC 风险的关系，并通过测量抗氧化剂谷胱甘肽（GSH）水平来研究 HCC 患者的氧化应激状态。本研究共纳入 99 例新诊断的 HCC 患者和 80 例健康个体作为正常对照组。所有参与者均按照 Ellman 法测量血浆 GSH 水平，并采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测 GSTP1 多态性 Ile105Val（rs1695 A > G）。

结果

在 HCC 患者中，GSTP1 突变纯合子或突变杂合子基因型的发生明显更高，而野生基因型在正常对照组中发生明显更高。突变 GSTP1 基因型、年龄较大、男性和高血清丙氨酸氨基转移酶（ALT）与 HCC 发展风险增加相关。当血浆 GSH 的截断值为 2003.5 μM/mg 时，GSH 的最佳灵敏度、特异性、阳性预测值（PPV）、阴性预测值（NPV）和总体诊断性能分别为 57.6%、52.5%、60%和 40%。GSH 的曲线下面积为 0.562。