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苏氨酸和酪氨酸激酶（TTK）在乳腺癌中的mRNA和蛋白质表达；新辅助治疗环境中的预后意义。

Threonine and tyrosine kinase (TTK) mRNA and protein expression in breast cancer; prognostic significance in the neoadjuvant setting.

作者信息

Ashi Abrar, Awaji Aeshah A, Bond Jacquelyn, Johnson Colin A, Shaaban Abeer M, Bell Sandra M

机构信息

Division of Molecular Medicine, Leeds Institute of Medical Research, St James's University Hospital, University of Leeds, Leeds, UK.

Histopathology, St James's Institute for Oncology, St James's University Hospital, Leeds, UK.

出版信息

Histopathology. 2025 May;86(6):916-932. doi: 10.1111/his.15399. Epub 2025 Jan 7.

DOI:10.1111/his.15399
PMID:39775836
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11964583/
Abstract

AIMS

Threonine and tyrosine kinase (TTK) is up-regulated in triple-negative breast cancer (TNBC), yet its expression in patients undergoing neoadjuvant chemotherapy (NACT) remains unexplored. This investigation aims to assess TTK protein expression in treatment-naïve pre-treatment cores and paired pre- and post-NACT breast cancer (BC) cohorts, as well as its correlation with microcephaly 1 (MCPH1) protein expression.

METHODS AND RESULTS

Transcriptomic data were sourced from the Gene Expression Omnibus microarray database for mRNA expression analysis. TTK protein expression was evaluated using immunohistochemistry staining, employing receiver operating characteristic curve analysis to determine an optimal TTK expression cut-off point. The association between TTK expression, clinicopathological parameters and survival outcomes was examined. Additionally, MCPH1 protein expression was assessed in a pilot study. Analysis revealed a significantly elevated TTK mRNA expression in BC tissue compared to normal breast tissue, with high TTK mRNA levels predicting reduced overall survival. Notably, TTK protein expression increased significantly post-NACT in a paired cohort. Conversely, decreased TTK protein expression pre-NACT was correlated with improved overall survival.

CONCLUSIONS

High TTK and low MCPH1 protein expression was significantly correlated, highlighting TTK's potential as a biomarker for BC and a therapeutic target for MCPH1-deficient cancer cells.

摘要

目的

苏氨酸和酪氨酸激酶（TTK）在三阴性乳腺癌（TNBC）中上调，但其在接受新辅助化疗（NACT）患者中的表达仍未得到探索。本研究旨在评估未经治疗的治疗前肿瘤组织芯以及配对的NACT治疗前后乳腺癌（BC）队列中TTK蛋白的表达情况，及其与小头畸形1（MCPH1）蛋白表达的相关性。

方法与结果

转录组数据来源于基因表达综合数据库（Gene Expression Omnibus）进行mRNA表达分析。采用免疫组织化学染色评估TTK蛋白表达，利用受试者工作特征曲线分析确定最佳TTK表达切点。检测TTK表达与临床病理参数及生存结果之间的关联。此外，在一项初步研究中评估了MCPH1蛋白表达。分析显示，与正常乳腺组织相比，BC组织中TTK mRNA表达显著升高，高TTK mRNA水平预示着总生存期缩短。值得注意的是，在配对队列中，NACT后TTK蛋白表达显著增加。相反，NACT前TTK蛋白表达降低与总生存期改善相关。

结论

高TTK和低MCPH1蛋白表达显著相关，突出了TTK作为BC生物标志物以及MCPH1缺陷癌细胞治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65b0/11964583/f88d7b77e115/HIS-86-916-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65b0/11964583/31673c05cab6/HIS-86-916-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65b0/11964583/6bb9154b9823/HIS-86-916-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65b0/11964583/6be286594770/HIS-86-916-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65b0/11964583/a426480f58d7/HIS-86-916-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65b0/11964583/3b5620a1bcb9/HIS-86-916-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65b0/11964583/f88d7b77e115/HIS-86-916-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65b0/11964583/31673c05cab6/HIS-86-916-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65b0/11964583/6bb9154b9823/HIS-86-916-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65b0/11964583/6be286594770/HIS-86-916-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65b0/11964583/a426480f58d7/HIS-86-916-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65b0/11964583/3b5620a1bcb9/HIS-86-916-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65b0/11964583/f88d7b77e115/HIS-86-916-g004.jpg

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The emerging role of MCPH1/BRIT1 in carcinogenesis.MCPH1/BRIT1在致癌作用中的新作用。
Front Oncol. 2023 Jan 31;13:1047588. doi: 10.3389/fonc.2023.1047588. eCollection 2023.
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Corrigendum to: Current practice and surgical outcomes of neoadjuvant chemotherapy for early breast cancer: UK NeST study.
《早期乳腺癌新辅助化疗的当前实践与手术结果：英国NeST研究》勘误
Br J Surg. 2022 Dec 13;110(1):124. doi: 10.1093/bjs/znac282.
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Neoplasma. 2022 Mar;69(2):274-282. doi: 10.4149/neo_2021_210421N541. Epub 2021 Nov 30.
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Breast Cancer Treatments: Updates and New Challenges.乳腺癌治疗：进展与新挑战
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Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.《全球癌症统计数据 2020：全球 185 个国家和地区 36 种癌症的发病率和死亡率估计》。
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