Oncotarget

Research Papers:

Quantitative proteome profiling stratifies fibroepithelial lesions of the breast

Aviral Kumar, David S. Nayakanti, Kiran K. Mangalaparthi, Veena Gopinath, Nandyala Venkat Narsimha Reddy, Krishna Govindan, Geeta Voolapalli, Prashant Kumar _ and Lekha Dinesh Kumar _

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Oncotarget. 2021; 12:507-518. https://doi.org/10.18632/oncotarget.27889

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Abstract

Aviral Kumar1,*, David S. Nayakanti2,5,*, Kiran K. Mangalaparthi2,#, Veena Gopinath1,#, Nandyala Venkat Narsimha Reddy3, Krishna Govindan4, Geeta Voolapalli3, Prashant Kumar2,5 and Lekha Dinesh Kumar1

1 Cancer Biology, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, 500007, India

2 Institute of Bioinformatics, Discoverer Building International Tech Park, Whitefield, Bangalore, 560066, India

3 Department of Surgery and Pathology, Gandhi Hospital, Secunderabad, 500025, India

4 Department of Pathology, Government Medical College, Thiruvananthapuram, Kerala, 695011, India

5 Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India

* Authors share equal first authorship

# Authors share equal second authorship

Correspondence to:

Lekha Dinesh Kumar,email: [email protected]
Prashant Kumar,email: [email protected]

Keywords: breast tumors; fibroepithelial lesions; phyllodes; iTRAQ; quantitative proteomics

Received: July 30, 2020     Accepted: January 26, 2021     Published: March 02, 2021

Copyright: © 2021 Kumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Breast fibroepithelial lesions (FELs) include heterogeneous pathological tumors, involving indolent fibroadenoma (FAD) to potentially aggressive phyllodes tumors (PTs). The current grading system remains unreliable in differentiating these tumors due to histological heterogeneity and lack of appropriate markers to monitor the sudden and unpredictable malignant transformation of PTs. Thus, there exists an imminent need for a marker-based diagnostic approach to augment the conventional histological platform that could lead to accurate diagnosis and distinction of FELs. The high- throughput quantitative proteomic analysis suggested that FAD and PTs form distinct clusters away from borderline and malignant though there exist marked differences between them. Interestingly, over-expression of extracellular matrices (ECM) related proteins and epithelial-mesenchymal transition (EMT) markers in borderline PTs led us to hypothesize a model of deposition and degradation leading to ECM remodeling and EMT acquisition triggering its malignant transformation. We also identified three candidate biomarkers such as MUCL1, HTRA1, and VEGDF uniquely expressed in FAD, borderline, and malignant PTs, respectively, which were further validated using immunohistochemistry. The present work shed light on a brief mechanistic framework of PTs aggressive nature and present potential biomarkers to differentiate overlapping FELs that would be of practical utility in augmenting existing diagnosis and disease management for this rare tumor.


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