Suppr超能文献

MT1G,一个新兴的铁死亡相关基因:前列腺癌中一个新的预后生物标志物和免疫治疗敏感性的指标。

MT1G, an emerging ferroptosis-related gene: A novel prognostic biomarker and indicator of immunotherapy sensitivity in prostate cancer.

机构信息

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

Environ Toxicol. 2024 Feb;39(2):927-941. doi: 10.1002/tox.23997. Epub 2023 Nov 16.

Abstract

BACKGROUND

Prostate cancer is a leading cause of cancer-related deaths in men worldwide. Despite advances in treatment strategies, there is still a need for novel therapeutic targets and approaches. Ferroptosis has emerged as a critical process in the development and progression of several cancers, including prostate cancer (PCA). In this study, we investigate the role of MT1G, a gene implicated in immune responses and ferroptosis, in the pathogenesis of PCA. Our objective is to elucidate its prognostic significance and its impact on the tumor microenvironment, while exploring its potential in enhancing the sensitivity to immune checkpoint inhibitor (ICI) therapy.

METHODS

We utilized a combination of in silico analysis and experimental techniques to investigate the role of MT1G in PCA. First, we analyzed large-scale genomic datasets to assess the expression pattern and prognostic significance of MT1G in PCA patients. Subsequently, we performed functional assays to explore the impact of MT1G in PCA and its potential involvement in modulating immune responses. In addition, we conducted in vivo experiments to evaluate the effect of MT1G on tumor growth and response to ICI therapy.

RESULTS

Our analysis revealed that MT1G expression is significantly downregulated in PCA tissues compared to normal prostate tissues and is associated with poor prognosis. Furthermore, MT1G overexpression inhibited the growth of PCA cells in vitro and in vivo. Importantly, we found that MT1G regulates the tumor microenvironment by modulating immune cell infiltration and inhibiting immunosuppressive factors. Furthermore, our study reveals a significant correlation between MT1G expression levels and the response to immune checkpoint inhibitor (ICI) therapy in prostate cancer (PCA) patients, as MT1G upregulation leads to an increase in PDL-1 expression. These findings underscore the potential of MT1G as a promising predictive biomarker for ICI therapy response in PCA patients.

CONCLUSION

Our study elucidates the pivotal role played by MT1G in the pathogenesis of prostate cancer (PCA) and its profound implications for prognosis. Moreover, it raises the intriguing possibility that MT1G could pave the way for novel therapeutic approaches in PCA treatment. This potential arises from its ability to orchestrate immune infiltration within the tumor microenvironment, consequently enhancing sensitivity to immune checkpoint inhibitor (ICI) therapy. Therefore, our findings hold substantial promise for advancing our comprehension of PCA and exploring innovative therapeutic strategies.

摘要

背景

前列腺癌是全球男性癌症相关死亡的主要原因。尽管治疗策略取得了进展,但仍需要新的治疗靶点和方法。铁死亡已成为包括前列腺癌(PCA)在内的几种癌症发生和发展的关键过程。在这项研究中,我们研究了 MT1G,一种与免疫反应和铁死亡有关的基因,在 PCA 发病机制中的作用。我们的目的是阐明其预后意义及其对肿瘤微环境的影响,同时探索其增强对免疫检查点抑制剂(ICI)治疗敏感性的潜力。

方法

我们结合了计算机分析和实验技术来研究 MT1G 在 PCA 中的作用。首先,我们分析了大规模基因组数据集,以评估 MT1G 在 PCA 患者中的表达模式和预后意义。随后,我们进行了功能分析,以探讨 MT1G 在 PCA 中的作用及其在调节免疫反应中的潜在作用。此外,我们进行了体内实验,以评估 MT1G 对肿瘤生长和对 ICI 治疗的反应的影响。

结果

我们的分析表明,与正常前列腺组织相比,MT1G 在 PCA 组织中的表达明显下调,并且与预后不良相关。此外,MT1G 过表达在体外和体内抑制了 PCA 细胞的生长。重要的是,我们发现 MT1G 通过调节免疫细胞浸润和抑制免疫抑制因子来调节肿瘤微环境。此外,我们的研究揭示了 MT1G 表达水平与前列腺癌(PCA)患者对免疫检查点抑制剂(ICI)治疗反应之间存在显著相关性,因为 MT1G 上调导致 PDL-1 表达增加。这些发现强调了 MT1G 作为 PCA 患者 ICI 治疗反应的有前途的预测生物标志物的潜力。

结论

我们的研究阐明了 MT1G 在前列腺癌(PCA)发病机制中的关键作用及其对预后的深远影响。此外,它提出了一个有趣的可能性,即 MT1G 可以为 PCA 治疗开辟新的治疗方法。这种潜力源于其在肿瘤微环境中协调免疫浸润的能力,从而增强对免疫检查点抑制剂(ICI)治疗的敏感性。因此,我们的发现为我们理解 PCA 并探索创新治疗策略提供了很大的希望。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验