Subcellular expression of MTA1, HIF1A and p53 in primary tumor predicts aggressive triple negative breast cancers: a meta-analysis based study

IF 2.9 4区生物学 Q3 CELL BIOLOGY

Journal of Molecular Histology Pub Date : 2024-04-13 DOI:10.1007/s10735-024-10190-9

Shanaz S Sharaf, K M Jaganath Krishna, Asha Lekshmi, Sujathan

{"title":"Subcellular expression of MTA1, HIF1A and p53 in primary tumor predicts aggressive triple negative breast cancers: a meta-analysis based study","authors":"Shanaz S Sharaf, K M Jaganath Krishna, Asha Lekshmi,  Sujathan","doi":"10.1007/s10735-024-10190-9","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>The prevalence of TNBC in India is higher compared to western countries. There is a multitude of biomarkers associated with different clinical outcomes of TNBC with contradictory reports. Identification of a set of specific biomarkers from the very many number of proteins reported in the literature to predict prognosis of TNBC is an urgent clinical need.</p><h3>Methodology</h3><p>A systematic review of key molecular biomarkers in cohort studies that have been investigated for their role in breast cancer prognosis was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. A meta-analysis was used to evaluate their pooled hazard ratio (HR) and the corresponding 95% confidence interval (95% CI) statistically. Immunohistochemical characterization of the meta-analyzed markers were performed in a cohort of 200 retrospective TNBC and 100 non TNBC patient tissues. Kaplan–Meier plot were used to evaluate disease free survival (DFS), and overall survival (OS). Cox regression models were used to evaluate predictors of DFS and OS.</p><h3>Results</h3><p>Using a meta-analytical approach, we consolidated the biomarker signatures associated with survival outcomes in breast cancers. The promising markers that emerged for the prediction of DFS and OS included E-Cadherin, Survivin, p53, MTA1, HIF1A, CD133, Vimentin and CK5/6. Evaluation of these markers in tumor tissue revealed that subcellular localization of p53, MTA1 and HIF1A had a significant association in predicting TNBC prognosis. Kaplan Meier plot revealed that p53 (OS <i>p</i> = 0.007, DFS <i>p</i> = 0.004), HIF 1 A (OS <i>p</i> = 0.054, DFS <i>p</i> = 0.009) and MTA1 (OS <i>p</i> = 0.043, DFS = <i>p</i> = 0.001) expression in the primary tumor tissue were found to be significantly correlated with poor OS and DFS, whereas expression of Survivin (DFS <i>p</i> = 0.024) and E Cadherin (DFS <i>p</i> = 0.027) correlated with DFS alone in TNBC. Univariate analysis revealed that p53, HIF1A and MTA1 could be independent prognostic markers.</p><h3>Conclusion</h3><p>Our study suggests cytoplasmic over expression of HIF1A, nuclear over expression of MTA1 and mutated p53 in the primary tumor tissue of TNBC have significance as markers predicting survival of TNBC patients.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Histology","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s10735-024-10190-9","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

The prevalence of TNBC in India is higher compared to western countries. There is a multitude of biomarkers associated with different clinical outcomes of TNBC with contradictory reports. Identification of a set of specific biomarkers from the very many number of proteins reported in the literature to predict prognosis of TNBC is an urgent clinical need.

Methodology

A systematic review of key molecular biomarkers in cohort studies that have been investigated for their role in breast cancer prognosis was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. A meta-analysis was used to evaluate their pooled hazard ratio (HR) and the corresponding 95% confidence interval (95% CI) statistically. Immunohistochemical characterization of the meta-analyzed markers were performed in a cohort of 200 retrospective TNBC and 100 non TNBC patient tissues. Kaplan–Meier plot were used to evaluate disease free survival (DFS), and overall survival (OS). Cox regression models were used to evaluate predictors of DFS and OS.

Results

Using a meta-analytical approach, we consolidated the biomarker signatures associated with survival outcomes in breast cancers. The promising markers that emerged for the prediction of DFS and OS included E-Cadherin, Survivin, p53, MTA1, HIF1A, CD133, Vimentin and CK5/6. Evaluation of these markers in tumor tissue revealed that subcellular localization of p53, MTA1 and HIF1A had a significant association in predicting TNBC prognosis. Kaplan Meier plot revealed that p53 (OS p = 0.007, DFS p = 0.004), HIF 1 A (OS p = 0.054, DFS p = 0.009) and MTA1 (OS p = 0.043, DFS = p = 0.001) expression in the primary tumor tissue were found to be significantly correlated with poor OS and DFS, whereas expression of Survivin (DFS p = 0.024) and E Cadherin (DFS p = 0.027) correlated with DFS alone in TNBC. Univariate analysis revealed that p53, HIF1A and MTA1 could be independent prognostic markers.

Conclusion

Our study suggests cytoplasmic over expression of HIF1A, nuclear over expression of MTA1 and mutated p53 in the primary tumor tissue of TNBC have significance as markers predicting survival of TNBC patients.

Abstract Image

查看原文本刊更多论文

原发性肿瘤中 MTA1、HIF1A 和 p53 的亚细胞表达可预测侵袭性三阴性乳腺癌：一项基于荟萃分析的研究

背景TNBC在印度的发病率高于西方国家。有许多生物标志物与 TNBC 的不同临床结果相关，但报道相互矛盾。从文献报道的大量蛋白质中找出一组特异性生物标志物来预测 TNBC 的预后是临床的迫切需要。研究方法对队列研究中的关键分子生物标志物进行了系统回顾，这些标志物在乳腺癌预后中的作用已得到研究。研究遵循了系统综述和荟萃分析首选报告项目（Preferred Reporting Items for Systematic Reviews and Meta-Analyses，PRISMA）方法。采用荟萃分析法对其汇总的危险比（HR）和相应的 95% 置信区间（95% CI）进行统计评估。对 200 例回顾性 TNBC 和 100 例非 TNBC 患者组织进行了荟萃分析标记物的免疫组化鉴定。采用 Kaplan-Meier 图评估无病生存期（DFS）和总生存期（OS）。结果通过荟萃分析方法，我们整合了与乳腺癌生存结果相关的生物标志物特征。在预测DFS和OS方面有希望的标志物包括E-Cadherin、Survivin、p53、MTA1、HIF1A、CD133、Vimentin和CK5/6。对肿瘤组织中这些标记物的评估显示，p53、MTA1和HIF1A的亚细胞定位与预测TNBC预后有显著关联。Kaplan Meier图显示，原发性肿瘤中p53（OS p = 0.007，DFS p = 0.004）、HIF 1 A（OS p = 0.054，DFS p = 0.009）和MTA1（OS p = 0.043，DFS = p = 0.001）的表达与不良OS和DFS显著相关，而Survivin（DFS p = 0.024）和E Cadherin（DFS p = 0.027）的表达仅与TNBC的DFS相关。单变量分析显示，p53、HIF1A和MTA1可能是独立的预后标志物。结论：我们的研究表明，TNBC原发肿瘤组织中HIF1A的胞浆过度表达、MTA1的核过度表达和突变的p53作为预测TNBC患者生存期的标志物具有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.