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雄激素受体基因突变与前列腺癌患者雄激素受体丝氨酸蛋白 A 复合物和谷胱甘肽 S-转移酶 T1 和 M1 拷贝数的关系。

Association of Androgen-Receptor Gene Mutations with the Copy Number of Androgen-Receptor Silk Protein A Complex and Glutathione-S-Transferases T1 and M1 in Prostate Cancer Patients.

机构信息

Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130022, China.

Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130022, China.

出版信息

Genet Res (Camb). 2023 Feb 14;2023:5956951. doi: 10.1155/2023/5956951. eCollection 2023.

Abstract

OBJECTIVE

The purpose of our work was to explore the association of mutations in the androgen receptor gene and copy numbers of the androgen-receptor silk protein A complex with glutathione-S-transferases T1 and M1 in prostate cancer patients.

MATERIALS AND METHODS

Eighty-five patients with PC and 85 healthy controls were included in the study. Fasting peripheral venous blood was collected, whole blood genomic DNA was extracted, and AR gene-receptor genotype was detected by a high-resolution melting curve analysis detection technology. Expression levels of androgen receptor (AR) and filamin protein A (FlnA) were detected by Western blotting. RT-PCR was used to detect the copy number of T1 and M1 glutathione-S-transferases.

RESULTS

The wild-type androgen receptor gene rs5918762 is of TT type. The frequencies of CC and TC genes in the prostate cancer group were significantly higher than those in the normal control group ( < 0.05). Compared with TT-type PC patients, PC patients with TC-type and CC-type had higher expression levels of sex hormone receptor silk protein A complex and higher copy numbers of GSTT1 and GSTM1 ( < 0.05). Androgen-receptor gene mutation (T ⟶ C) was significantly positively correlated with the expression level of androgen-receptor silk protein A complex and the copy number of GSTT1 and GSTM1.

CONCLUSION

Androgen-receptor gene polymorphisms were significantly associated with expression levels of androgen receptor complex and silk proteins, and copy numbers of T1 and M1 glutathione-S-transferases. A combination of four factors can be used to identify prostate cancer susceptibility and disease progression.

摘要

目的

本研究旨在探讨雄激素受体基因突变和雄激素受体丝氨酸蛋白 A 复合物与谷胱甘肽 S-转移酶 T1 和 M1 的拷贝数与前列腺癌患者之间的关联。

材料与方法

纳入 85 例 PC 患者和 85 例健康对照者。采集空腹外周静脉血,提取全血基因组 DNA,采用高分辨率熔解曲线分析检测技术检测 AR 基因-受体基因型。通过 Western blot 检测雄激素受体(AR)和丝氨酸蛋白 A(FlnA)的表达水平。采用 RT-PCR 检测 T1 和 M1 谷胱甘肽 S-转移酶的拷贝数。

结果

野生型雄激素受体基因 rs5918762 为 TT 型。前列腺癌组的 CC 和 TC 基因频率明显高于正常对照组(<0.05)。与 TT 型 PC 患者相比,TC 型和 CC 型 PC 患者的性激素受体丝氨酸蛋白 A 复合物表达水平更高,GSTT1 和 GSTM1 的拷贝数更高(<0.05)。雄激素受体基因突变(T ⟶ C)与雄激素受体丝氨酸蛋白 A 复合物的表达水平和 GSTT1 和 GSTM1 的拷贝数呈显著正相关。

结论

雄激素受体基因多态性与雄激素受体复合物和丝氨酸蛋白的表达水平以及 T1 和 M1 谷胱甘肽 S-转移酶的拷贝数显著相关。这四个因素的组合可用于鉴定前列腺癌的易感性和疾病进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6729/9943596/22f147a6829d/GR2023-5956951.001.jpg

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