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蛋白质组学分析人类子宫内膜组织揭示了 PI3K/AKT/mTOR 通路和肿瘤血管生成分子在子宫内膜癌发病机制中的作用。

Proteomic Analysis of Human Endometrial Tissues Reveals the Roles of PI3K/AKT/mTOR Pathway and Tumor Angiogenesis Molecules in the Pathogenesis of Endometrial Cancer.

机构信息

Department of Obstetrics & Gynecology, Tianjin Medical University, Tianjin 300070, China.

Department of Gynecology, Chifeng Municipal Hospital, Chifeng Clinical Medical School of Inner Mongolia Medical University, Chifeng 024000, China.

出版信息

Biomed Res Int. 2020 Aug 22;2020:5273969. doi: 10.1155/2020/5273969. eCollection 2020.

Abstract

As one major gynecological malignancy, endometrial cancer (EC) has been widely studied recently. However, its pathogenesis is still unclear to date. In this study, we identified differentially expressed proteins between 30 endometrial cancer tissues and 30 matched normal controls using 2D LC-MS/MS quantitative proteomics. As a result, we identified 619 differentially expressed proteins among all 2521 proteins being quantified. Further analyses suggested that the changes of fat, amino acid metabolism, peroxisome, extracellular signal, cytoskeleton, and other signaling or metabolic pathways may be closely related to the development of this cancer. Particularly, the PI3K/AKT/mTOR pathway-related molecules including PI3K and mTOR, ERK (the molecule of the ERK pathway), SPP1, and ANGPT2 (angiogenesis-related molecules) are highly associated with the pathogenesis of EC, which were reconfirmed by western blot and immunohistochemistry (IHC) analysis. In summary, our study revealed that the PI3K/AKT/mTOR pathway and tumor angiogenesis molecules contribute to the pathogenesis of endometrial cancer.

摘要

作为一种主要的妇科恶性肿瘤,子宫内膜癌(EC)最近得到了广泛研究。然而,其发病机制迄今仍不清楚。在这项研究中,我们使用二维液相色谱-串联质谱定量蛋白质组学技术,鉴定了 30 例子宫内膜癌组织和 30 例匹配的正常对照之间的差异表达蛋白。结果,我们在所有被定量的 2521 种蛋白质中鉴定出 619 种差异表达蛋白。进一步分析表明,脂肪、氨基酸代谢、过氧化物酶体、细胞外信号、细胞骨架和其他信号或代谢途径的变化可能与这种癌症的发展密切相关。特别是,PI3K/AKT/mTOR 通路相关分子,包括 PI3K 和 mTOR、ERK(ERK 通路的分子)、SPP1 和 ANGPT2(血管生成相关分子),与 EC 的发病机制高度相关,这通过 Western blot 和免疫组织化学(IHC)分析得到了进一步证实。总之,我们的研究揭示了 PI3K/AKT/mTOR 通路和肿瘤血管生成分子有助于子宫内膜癌的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fa9/7463404/ca7ecead7cdc/BMRI2020-5273969.001.jpg

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