Comprehensive Analysis of the Relationship between Cuproptosis-Related Gene GCSH and Prognosis, Tumor Microenvironment Infiltration, and Therapy Response in Endometrial Cancer.

IF 2.5 3区 医学 Q3 ONCOLOGY Oncology Pub Date : 2024-01-01 Epub Date: 2023-10-12 DOI:10.1159/000534018
Mengya Zhao, Haihang Nie, Peishan Qiu, Yali Yu, Haizhou Wang, Fan Wang, Jun Fang, Qiu Zhao
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Abstract

Introduction: Cuproptosis is a novel form of cell death regulated by protein lipoylation and implicated in mitochondrial metabolism. However, further research is needed to explore the influence of the cuproptosis-related gene γ-glutamylcysteine synthetase (GCSH) on the prognosis of endometrial cancer (EC), the tumor immune microenvironment, and therapeutic response.

Methods: The differential expression of GCSH between EC and normal tissues was analyzed using multiple public databases. Additionally, cancer and adjacent tissues were prospectively collected from 17 EC patients, and immunohistochemical analysis was performed to further investigate GCSH expression differences. The relationship between GCSH and the prognosis and clinicopathological characteristics of EC patients was evaluated, and a nomogram was constructed to predict patient survival based on GCSH expression. Subsequently, Gene set variation analysis was used to explore the potential biological functions of GCSH in EC. The impact of GCSH on the tumor microenvironment (TME) was estimated. Finally, the effect of GCSH on the response to immunotherapy and chemotherapeutic drugs in EC was investigated.

Results: The expression of GCSH was significantly upregulated in EC. High GCSH expression was associated with poor prognosis in EC patients. Enrichment analysis revealed an association between high GCSH and immune suppression. Furthermore, high GCSH was found to be associated with a non-inflamed TME, leading to decreased infiltration levels of immune cells. Lastly, it was observed that patients with high GCSH exhibited insensitivity to both immunotherapy and chemotherapeutic drugs.

Conclusion: This study revealed the role of GCSH in TME, response to therapy, and clinical prognosis in EC, which provided novel insights for the therapeutic application in EC.

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子宫内膜癌症铜中毒相关基因GCSH与预后、肿瘤微环境浸润和治疗反应的关系综合分析。
背景:杯状细胞病是一种新型的细胞死亡形式,受蛋白质脂质化调节,与线粒体代谢有关。然而,铜中毒相关基因γ-谷氨酰半胱氨酸合成酶(GCSH)对子宫内膜癌症(EC)预后、肿瘤免疫微环境和治疗反应的影响仍有待进一步研究。方法:利用多个公共数据库分析癌症子宫内膜组织和正常组织中GCSH的差异表达。此外,从17名EC患者中前瞻性收集癌症和邻近组织,并进行免疫组织化学分析以进一步研究GCSH表达差异。评估了GCSH与EC患者预后和临床病理特征之间的关系,并根据GCSH的表达构建了预测患者生存率的列线图。然后,利用基因集变异分析(GSVA)来探索GCSH在EC中的潜在生物学功能。估计GCSH对肿瘤微环境(TME)的影响。最后,研究了GCSH对EC免疫治疗和化疗药物反应的影响。结果:GCSH在EC中的表达显著上调。GCSH的高表达与EC患者的预后不良有关。富集分析表明,高GCSH与免疫抑制有关。此外,发现高GCSH与未发炎的TME有关,导致免疫细胞浸润水平降低。最后,观察到高GCSH患者对免疫疗法和化疗药物都不敏感。结论:本研究揭示了GCSH在EC TME、治疗反应和临床预后中的作用,为EC的治疗应用提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Oncology
Oncology 医学-肿瘤学
CiteScore
6.00
自引率
2.90%
发文量
76
审稿时长
6-12 weeks
期刊介绍: Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.
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