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卵巢癌中谷胱甘肽S-转移酶Mu(GSTM)基因家族的综合分析确定了其预后及表达意义。

Comprehensive analysis of the glutathione S-transferase Mu (GSTM) gene family in ovarian cancer identifies prognostic and expression significance.

作者信息

Zhang Juan, Li Yan, Zou Juan, Lai Chun-Tian, Zeng Tian, Peng Juan, Zou Wen-da, Cao Bei, Liu Dan, Zhu Li-Yu, Li Hui, Li Yu-Kun

机构信息

Department of Assisted Reproductive Centre, Zhuzhou central hospital, Xiangya hospital Zhuzhou central south university, Central south university, Zhuzhou, China.

Hunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, University of South China, Hengyang, China.

出版信息

Front Oncol. 2022 Jul 28;12:968547. doi: 10.3389/fonc.2022.968547. eCollection 2022.

Abstract

BACKGROUND

Ovarian cancer (OC) is one of the most common types of gynecologic tumor over the world. The Glutathione S-transferase Mu (GSTM) has five members, including GSTM1-5. These GSTMs is involved in cell metabolism and detoxification, but their role in OC remains unknown.

METHODS

Data from multiple public databases associated with OC and GSTMs were collected. Expression, prognosis, function enrichment, immune infiltration, stemness index, and drug sensitivity analysis was utilized to identify the roles of GSTMs in OC progression. RT-qPCR analysis confirmed the effect of AICAR, AT-7519, PHA-793887 and PI-103 on the mRNA levels of GSTM3/4.

RESULTS

GSTM1-5 were decreased in OC samples compared to normal ovary samples. GSTM1/5 were positively correlated with OC prognosis, but GSTM3 was negatively correlated with OC prognosis. Function enrichment analysis indicated GSTMs were involved in glutathione metabolism, drug metabolism, and drug resistance. Immune infiltration analysis indicated GSTM2/3/4 promoted immune escape in OC. GSTM5 was significantly correlated with OC stemness index. GSTM3/4 were remarkedly associated with OC chemoresistance, especially in AICAR, AT-7519, PHA-793887 and PI-103.

CONCLUSION

GSTM3 was negatively correlated with OC prognosis, and associated with OC chemoresistance and immune escape. This gene may serve as potential prognostic biomarkers and therapeutic target for OC patients.

摘要

背景

卵巢癌(OC)是全球最常见的妇科肿瘤类型之一。谷胱甘肽S-转移酶Mu(GSTM)有五个成员,包括GSTM1-5。这些GSTM参与细胞代谢和解毒,但其在OC中的作用尚不清楚。

方法

收集来自多个与OC和GSTM相关的公共数据库的数据。利用表达、预后、功能富集、免疫浸润、干性指数和药物敏感性分析来确定GSTM在OC进展中的作用。RT-qPCR分析证实了AICAR、AT-7519、PHA-793887和PI-103对GSTM3/4 mRNA水平的影响。

结果

与正常卵巢样本相比,OC样本中GSTM1-5表达降低。GSTM1/5与OC预后呈正相关,但GSTM3与OC预后呈负相关。功能富集分析表明GSTM参与谷胱甘肽代谢、药物代谢和耐药性。免疫浸润分析表明GSTM2/3/4促进OC中的免疫逃逸。GSTM5与OC干性指数显著相关。GSTM3/4与OC化疗耐药显著相关,尤其是在AICAR、AT-7519、PHA-793887和PI-103中。

结论

GSTM3与OC预后呈负相关,并与OC化疗耐药和免疫逃逸相关。该基因可能作为OC患者潜在的预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03ef/9366399/3f5f0d373fe6/fonc-12-968547-g003.jpg

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