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SULF1的高表达与乳腺癌脑转移的不良预后相关。

High expression of SULF1 is associated with adverse prognosis in breast cancer brain metastasis.

作者信息

Li Yitong, Feng Tingting, Wang Qinghong, Wu Yue, Wang Jue, Zhang Wenlong, Kong Qi

机构信息

NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing, China.

出版信息

Animal Model Exp Med. 2025 Jan;8(1):162-170. doi: 10.1002/ame2.12406. Epub 2024 Apr 8.

Abstract

BACKGROUND

Breast cancer is the most common cancer in women, and in advanced stages, it often metastasizes to the brain. However, research on the biological mechanisms of breast cancer brain metastasis and potential therapeutic targets are limited.

METHODS

Differential gene expression analysis (DEGs) for the datasets GSE43837 and GSE125989 from the GEO database was performed using online analysis tools such as GEO2R and Sangerbox. Further investigation related to SULF1 was conducted using online databases such as Kaplan-Meier Plotter and cBioPortal. Thus, expression levels, variations, associations with HER2, biological processes, and pathways involving SULF1 could be analyzed using UALCAN, cBioPortal, GEPIA2, and LinkedOmics databases. Moreover, the sensitivity of SULF1 to existing drugs was explored using drug databases such as RNAactDrug and CADSP.

RESULTS

High expression of SULF1 was associated with poor prognosis in advanced breast cancer brain metastasis and was positively correlated with the expression of HER2. In the metastatic breast cancer population, SULF1 ranked top among the 16 DEGs with the highest mutation rate, reaching 11%, primarily due to amplification. KEGG and GSEA analyses revealed that the genes co-expressed with SULF1 were positively enriched in the 'ECM-receptor interaction' gene set and negatively enriched in the 'Ribosome' gene set. Currently, docetaxel and vinorelbine can act as treatment options if the expression of SULF1 is high.

CONCLUSIONS

This study, through bioinformatics analysis, unveiled SULF1 as a potential target for treating breast cancer brain metastasis (BM).

摘要

背景

乳腺癌是女性最常见的癌症,在晚期,它常转移至脑部。然而,关于乳腺癌脑转移的生物学机制及潜在治疗靶点的研究有限。

方法

使用诸如GEO2R和Sangerbox等在线分析工具,对来自基因表达综合数据库(GEO)的数据集GSE43837和GSE125989进行差异基因表达分析(DEGs)。使用诸如Kaplan-Meier Plotter和cBioPortal等在线数据库,对与硫酸酯酶1(SULF1)相关的内容进行进一步研究。因此,可使用UALCAN、cBioPortal、GEPIA2和LinkedOmics数据库分析SULF1的表达水平、变异情况、与人类表皮生长因子受体2(HER2)的关联、生物学过程以及相关通路。此外,使用诸如RNAactDrug和CADSP等药物数据库,探索SULF1对现有药物的敏感性。

结果

SULF1的高表达与晚期乳腺癌脑转移的不良预后相关,且与HER2的表达呈正相关。在转移性乳腺癌人群中,SULF1在16个突变率最高的差异基因中排名第一,达到11%,主要原因是扩增。京都基因与基因组百科全书(KEGG)和基因集富集分析(GSEA)表明,与SULF1共表达的基因在“细胞外基质受体相互作用”基因集中呈正富集,而在“核糖体”基因集中呈负富集。目前,如果SULF1表达较高,多西他赛和长春瑞滨可作为治疗选择。

结论

本研究通过生物信息学分析,揭示SULF1作为治疗乳腺癌脑转移(BM)的潜在靶点。

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