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

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Journal of Molecular Histology Aims and scope Submit manuscript

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.

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Acknowledgements

The authors wish to acknowledge CSIR for providing fellowship to SSS.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and publication of this article: This research was funded by DBT, grant number BT/PR18812/COE/34/01/2017, dated 19-05-2017.

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Authors and Affiliations

  1. Laboratory of Molecular Cytopathology and Proteomics, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, Kerala, India

    Shanaz S Sharaf, Asha Lekshmi &  Sujathan

  2. Manipal Academy of Higher Education, Karnataka, India

    Shanaz S Sharaf

  3. Epidemiology and Statistics Department, Regional Cancer Centre, Thiruvananthapuram, Kerala, India

    K M Jaganath Krishna

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  1. Shanaz S Sharaf
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  2. K M Jaganath Krishna
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  3. Asha Lekshmi
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  4. Sujathan
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Contributions

KS supervised the experiments and reviewed the manuscript. SSS performed experiments and drafted the manuscript. JK supported statistics and provided essential knowledge on statistical methods. AL edited the manuscript. All authors reviewed the final manuscript.

Corresponding author

Correspondence to Sujathan.

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Ethics approval and consent to participate

All experiments were approved by the committee for Research and Ethics of the local authorities The Institutional Review Board (IRB No. 06/2017/02) and the Human ethical committee of the Regional Cancer Centre (HEC 20/2017) have approved the study.

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The authors declared no potential conflicts of interest concerning this article’s research, authorship, and publication.

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Sharaf, S.S., Jaganath Krishna, K.M., Lekshmi, A. et al. Subcellular expression of MTA1, HIF1A and p53 in primary tumor predicts aggressive triple negative breast cancers: a meta-analysis based study. J Mol Histol (2024). https://doi.org/10.1007/s10735-024-10190-9

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  • DOI: https://doi.org/10.1007/s10735-024-10190-9

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