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基于转录组学鉴定与乳腺癌高转移潜能相关的关键肌动蛋白结合蛋白

Transcriptome-based identification of key actin-binding proteins associated with high metastatic potential in breast cancer.

作者信息

Müller Christian, Oliveira-Ferrer Leticia, Müller Volkmar, Schmalfeldt Barbara, Windhorst Sabine

机构信息

Bioinformatics Core, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

出版信息

Front Mol Biosci. 2024 Aug 30;11:1440276. doi: 10.3389/fmolb.2024.1440276. eCollection 2024.

DOI:10.3389/fmolb.2024.1440276
PMID:39281318
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11392851/
Abstract

INTRODUCTION

Actin-binding proteins (ABPs) are essential for the regulation of morphological plasticity required for tumor cells to metastasize. The aim of this study was to perform an unbiased bioinformatic approach to identify the key ABPs significantly associated with the metastatic potential of breast cancer cells.

METHODS

Microarray data from 181 primary breast cancer samples from our hospital were used, and all genes belonging to the Gene Ontology term actin cytoskeleton organization were obtained from QuickGO. Association with metastasis-free survival probability was tested using Cox proportional hazards regression, and pairwise co-expression was tested by Pearson correlations. Differential expression between different subgroups was analyzed using Wilcoxon tests for dichotomous traits and Kruskal-Wallis tests for categorical traits. Validation was performed using four publicly available breast cancer datasets.

RESULTS

was significantly associated with a low metastatic potential, and , , and were significantly associated with a high metastatic potential. A significantly higher expression of , and mRNA was found in the more aggressive Her2-positive and triple-negative subtypes as well as in ER-negative samples. Also, these genes were co-expressed in the same tumors. However, only mRNA levels of were increased in pN1 compared to pN0 patients. External validation revealed that and had significant associations with consistent hazard ratios in two breast cancer cohorts, and among these, exhibited the highest hazard ratios.

CONCLUSION

showed the strongest correlation with the metastatic potential of breast tumors. Thus, targeted inhibition of might be a promising approach to treat malignant breast cancer cells.

摘要

引言

肌动蛋白结合蛋白（ABPs）对于调节肿瘤细胞转移所需的形态可塑性至关重要。本研究的目的是采用一种无偏倚的生物信息学方法，以识别与乳腺癌细胞转移潜能显著相关的关键ABPs。

方法

使用了来自我院的181例原发性乳腺癌样本的微阵列数据，并且从QuickGO获取了属于基因本体术语“肌动蛋白细胞骨架组织”的所有基因。使用Cox比例风险回归测试与无转移生存概率的关联，并通过Pearson相关性测试成对共表达。使用Wilcoxon检验分析二分性状的不同亚组之间的差异表达，使用Kruskal-Wallis检验分析分类性状的差异表达。使用四个公开可用的乳腺癌数据集进行验证。

结果

[此处原文未明确指出具体是什么与低转移潜能显著相关，翻译时保留原文格式]与低转移潜能显著相关，而[此处原文未明确指出具体是什么与高转移潜能显著相关，翻译时保留原文格式]与高转移潜能显著相关。在侵袭性更强的Her2阳性和三阴性亚型以及ER阴性样本中，发现[此处原文未明确指出具体是什么基因，翻译时保留原文格式]、[此处原文未明确指出具体是什么基因，翻译时保留原文格式]和[此处原文未明确指出具体是什么基因，翻译时保留原文格式]的mRNA表达显著更高。此外，这些基因在同一肿瘤中共表达。然而，与pN0患者相比，pN1患者中只有[此处原文未明确指出具体是什么基因，翻译时保留原文格式]的mRNA水平升高。外部验证显示，[此处原文未明确指出具体是什么基因，翻译时保留原文格式]和[此处原文未明确指出具体是什么基因，翻译时保留原文格式]在两个乳腺癌队列中与一致的风险比具有显著关联，其中，[此处原文未明确指出具体是什么基因，翻译时保留原文格式]表现出最高的风险比。

结论

[此处原文未明确指出具体是什么与乳腺肿瘤的转移潜能显示出最强的相关性，翻译时保留原文格式]与乳腺肿瘤的转移潜能显示出最强的相关性。因此，靶向抑制[此处原文未明确指出具体是什么，翻译时保留原文格式]可能是治疗恶性乳腺癌细胞的一种有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a40/11392851/99de4f95186e/fmolb-11-1440276-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a40/11392851/4532456aa3d1/fmolb-11-1440276-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a40/11392851/018094e88ee0/fmolb-11-1440276-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a40/11392851/13806095fb99/fmolb-11-1440276-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a40/11392851/0a95775c356e/fmolb-11-1440276-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a40/11392851/418705694e3a/fmolb-11-1440276-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a40/11392851/99de4f95186e/fmolb-11-1440276-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a40/11392851/4532456aa3d1/fmolb-11-1440276-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a40/11392851/018094e88ee0/fmolb-11-1440276-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a40/11392851/13806095fb99/fmolb-11-1440276-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a40/11392851/0a95775c356e/fmolb-11-1440276-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a40/11392851/418705694e3a/fmolb-11-1440276-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a40/11392851/99de4f95186e/fmolb-11-1440276-g006.jpg

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