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原发性与放疗相关的乳腺血管肉瘤之间潜在关键基因和通路的差异。

Differences in potential key genes and pathways between primary and radiation-associated angiosarcoma of the breast.

作者信息

Wei Yuanfeng, Yang Xi, Gao Limin, Xu Yong, Yi Cheng

机构信息

Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.

Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Transl Oncol. 2022 May;19:101385. doi: 10.1016/j.tranon.2022.101385. Epub 2022 Mar 6.

Abstract

BACKGROUND

Angiosarcoma of the breast is a high-grade malignant soft tissue tumor, it can be divided into primary and radiation-associated angiosarcoma(secondary). However, the differences between primary and secondary angiosarcomas in terms of pathogenesis, clinical behavior, early diagnosis biomarkers, genetic abnormalities, and therapeutic targets remain to be fully elucidated. At the same time, due to its rarity, most of current information relating to angiosarcoma is provided by case reports. Therefore, exploring the mechanisms of primary and secondary breast angiosarcoma have important value for the discovery of new biomarkers and research into potential therapeutic targets.

METHODS

The differentially expressed genes (DEGs) between 36 cases of primary angiosarcoma and 54 cases of secondary angiosarcoma were screened. Then, the DEGs were used to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Then, a protein-protein interaction (PPI) network was constructed using the STRING database.

RESULTS

A total of 18 DEGs were identified, of which 13 were upregulated and 5 were downregulated in secondary breast angiosarcoma. The GO enrichment analysis showed that the DEGs were most enriched in metabolism, energy pathways, and protein metabolism in biological processes. The enriched signaling pathways of DEGs were the transforming growth factor-β (TGF-β), Wnt, Hippo and PI3K-Akt signaling pathways. Then, the PPI network was conducted and hub genes were identified and they were involved in thyroid hormone, Hippo and other signaling pathways.

CONCLUSION

This study lay the foundation for the discovery of effective and reliable molecular biomarkers and essential therapeutic targets for these malignancies.

摘要

背景

乳腺血管肉瘤是一种高级别恶性软组织肿瘤,可分为原发性和放疗相关性血管肉瘤(继发性)。然而,原发性和继发性血管肉瘤在发病机制、临床行为、早期诊断生物标志物、基因异常和治疗靶点方面的差异仍有待充分阐明。同时,由于其罕见性,目前有关血管肉瘤的大部分信息都是由病例报告提供的。因此,探索原发性和继发性乳腺血管肉瘤的发病机制对于发现新的生物标志物和研究潜在的治疗靶点具有重要价值。

方法

筛选36例原发性血管肉瘤和54例继发性血管肉瘤之间的差异表达基因(DEG)。然后,将这些DEG用于基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。接着,使用STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络。

结果

共鉴定出18个DEG,其中13个在继发性乳腺血管肉瘤中上调,5个下调。GO富集分析表明,这些DEG在生物过程中的代谢、能量途径和蛋白质代谢方面富集程度最高。DEG富集的信号通路是转化生长因子-β(TGF-β)、Wnt、Hippo和PI3K-Akt信号通路。然后,构建了PPI网络并鉴定出枢纽基因,它们参与甲状腺激素、Hippo等信号通路。

结论

本研究为发现这些恶性肿瘤有效且可靠的分子生物标志物和关键治疗靶点奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e687/8905315/40acdcf4b2c6/gr1.jpg

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