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多组学分析揭示了一型和二型子宫内膜癌中常见的失调通路。

A Multi-Omics Approach Revealed Common Dysregulated Pathways in Type One and Type Two Endometrial Cancers.

机构信息

Institute for Maternal and Child Health, IRCCS Institute for Maternal and Child Health-IRCCS Burlo Garofolo, 34137 Trieste, Italy.

Department of Pharmacy, University of Salerno, 84084 Salerno, Italy.

出版信息

Int J Mol Sci. 2023 Nov 7;24(22):16057. doi: 10.3390/ijms242216057.

Abstract

Endometrial cancer (EC) is the most frequent gynecologic cancer in postmenopausal women. Pathogenetic mechanisms that are related to the onset and progression of the disease are largely still unknown. A multi-omics strategy can help identify altered pathways that could be targeted for improving therapeutical approaches. In this study we used a multi-omics approach on four EC cell lines for the identification of common dysregulated pathways in type 1 and 2 ECs. We analyzed proteomics and metabolomics of AN3CA, HEC1A, KLE and ISHIKAWA cell lines by mass spectrometry. The bioinformatic analysis identified 22 common pathways that are in common with both types of EC. In addition, we identified five proteins and 13 metabolites common to both types of EC. Western blotting analysis on 10 patients with type 1 and type 2 EC and 10 endometria samples confirmed the altered abundance of NPEPPS. Our multi-omics analysis identified dysregulated proteins and metabolites involved in EC tumor growth. Further studies are needed to understand the role of these molecules in EC. Our data can shed light on common pathways to better understand the mechanisms involved in the development and growth of EC, especially for the development of new therapies.

摘要

子宫内膜癌(EC)是绝经后妇女最常见的妇科癌症。与疾病发生和进展相关的发病机制在很大程度上仍不清楚。多组学策略可以帮助识别可能针对改善治疗方法的改变途径。在这项研究中,我们使用了一种多组学方法对四种 EC 细胞系进行分析,以鉴定 1 型和 2 型 EC 中常见的失调途径。我们通过质谱法分析了 AN3CA、HEC1A、KLE 和 ISHIKAWA 细胞系的蛋白质组学和代谢组学。生物信息学分析确定了 22 个与两种类型的 EC 都共同存在的常见途径。此外,我们还鉴定了两种类型的 EC 共有的 5 种蛋白质和 13 种代谢物。对 10 例 1 型和 2 型 EC 患者和 10 例子宫内膜样本进行的 Western blot 分析证实了 NPEPPS 的丰度改变。我们的多组学分析鉴定了参与 EC 肿瘤生长的失调蛋白和代谢物。需要进一步研究这些分子在 EC 中的作用。我们的数据可以阐明共同途径,以更好地理解 EC 发展和生长中涉及的机制,特别是为新疗法的开发提供思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/148e/10671314/77ce16ff3283/ijms-24-16057-g001.jpg

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