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Delineation of Pathogenomic Insights of Breast Cancer in Young Women

The prognosis of breast cancer (BC) in young women (BCYW) aged ≤40 years tends to be poorer than that in older patients due to aggressive phenotypes, late diagnosis, distinct biologic, and poorly understood genomic features of BCYW. Considering the estimated predisposition of only approximately 15%...

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Autores principales: Paul, Aswathy Mary, George, Bijesh, Saini, Sunil, Pillai, Madhavan Radhakrishna, Toi, Masakazu, Costa, Luis, Kumar, Rakesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221490/
https://www.ncbi.nlm.nih.gov/pubmed/35741056
http://dx.doi.org/10.3390/cells11121927
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author Paul, Aswathy Mary
George, Bijesh
Saini, Sunil
Pillai, Madhavan Radhakrishna
Toi, Masakazu
Costa, Luis
Kumar, Rakesh
author_facet Paul, Aswathy Mary
George, Bijesh
Saini, Sunil
Pillai, Madhavan Radhakrishna
Toi, Masakazu
Costa, Luis
Kumar, Rakesh
author_sort Paul, Aswathy Mary
collection PubMed
description The prognosis of breast cancer (BC) in young women (BCYW) aged ≤40 years tends to be poorer than that in older patients due to aggressive phenotypes, late diagnosis, distinct biologic, and poorly understood genomic features of BCYW. Considering the estimated predisposition of only approximately 15% of the BC population to BC-promoting genes, the underlying reasons for an increased occurrence of BCYW, at large, cannot be completely explained based on general risk factors for BC. This underscores the need for the development of next-generation of tissue- and body fluid-based prognostic and predictive biomarkers for BCYW. Here, we identified the genes associated with BCYW with a particular focus on the age, intrinsic BC subtypes, matched normal or normal breast tissues, and BC laterality. In young women with BC, we observed dysregulation of age-associated cancer-relevant gene sets in both cancer and normal breast tissues, sub-sets of which substantially affected the overall survival (OS) or relapse-free survival (RFS) of patients with BC and exhibited statically significant correlations with several gene modules associated with cellular processes such as the stroma, immune responses, mitotic progression, early response, and steroid responses. For example, high expression of COL1A2, COL5A2, COL5A1, NPY1R, and KIAA1644 mRNAs in the BC and normal breast tissues from young women correlated with a substantial reduction in the OS and RFS of BC patients with increased levels of these exemplified genes. Many of the genes upregulated in BCYW were overexpressed or underexpressed in normal breast tissues, which might provide clues regarding the potential involvement of such genes in the development of BC later in life. Many of BCYW-associated gene products were also found in the extracellular microvesicles/exosomes secreted from breast and other cancer cell-types as well as in body fluids such as urine, saliva, breast milk, and plasma, raising the possibility of using such approaches in the development of non-invasive, predictive and prognostic biomarkers. In conclusion, the findings of this study delineated the pathogenomics of BCYW, providing clues for future exploration of the potential predictive and prognostic importance of candidate BCYW molecules and research strategies as well as a rationale to undertake a prospective clinical study to examine some of testable hypotheses presented here. In addition, the results presented here provide a framework to bring out the importance of geographical disparities, to overcome the current bottlenecks in BCYW, and to make the next quantum leap for sporadic BCYW research and treatment.
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spelling pubmed-92214902022-06-24 Delineation of Pathogenomic Insights of Breast Cancer in Young Women Paul, Aswathy Mary George, Bijesh Saini, Sunil Pillai, Madhavan Radhakrishna Toi, Masakazu Costa, Luis Kumar, Rakesh Cells Article The prognosis of breast cancer (BC) in young women (BCYW) aged ≤40 years tends to be poorer than that in older patients due to aggressive phenotypes, late diagnosis, distinct biologic, and poorly understood genomic features of BCYW. Considering the estimated predisposition of only approximately 15% of the BC population to BC-promoting genes, the underlying reasons for an increased occurrence of BCYW, at large, cannot be completely explained based on general risk factors for BC. This underscores the need for the development of next-generation of tissue- and body fluid-based prognostic and predictive biomarkers for BCYW. Here, we identified the genes associated with BCYW with a particular focus on the age, intrinsic BC subtypes, matched normal or normal breast tissues, and BC laterality. In young women with BC, we observed dysregulation of age-associated cancer-relevant gene sets in both cancer and normal breast tissues, sub-sets of which substantially affected the overall survival (OS) or relapse-free survival (RFS) of patients with BC and exhibited statically significant correlations with several gene modules associated with cellular processes such as the stroma, immune responses, mitotic progression, early response, and steroid responses. For example, high expression of COL1A2, COL5A2, COL5A1, NPY1R, and KIAA1644 mRNAs in the BC and normal breast tissues from young women correlated with a substantial reduction in the OS and RFS of BC patients with increased levels of these exemplified genes. Many of the genes upregulated in BCYW were overexpressed or underexpressed in normal breast tissues, which might provide clues regarding the potential involvement of such genes in the development of BC later in life. Many of BCYW-associated gene products were also found in the extracellular microvesicles/exosomes secreted from breast and other cancer cell-types as well as in body fluids such as urine, saliva, breast milk, and plasma, raising the possibility of using such approaches in the development of non-invasive, predictive and prognostic biomarkers. In conclusion, the findings of this study delineated the pathogenomics of BCYW, providing clues for future exploration of the potential predictive and prognostic importance of candidate BCYW molecules and research strategies as well as a rationale to undertake a prospective clinical study to examine some of testable hypotheses presented here. In addition, the results presented here provide a framework to bring out the importance of geographical disparities, to overcome the current bottlenecks in BCYW, and to make the next quantum leap for sporadic BCYW research and treatment. MDPI 2022-06-15 /pmc/articles/PMC9221490/ /pubmed/35741056 http://dx.doi.org/10.3390/cells11121927 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Paul, Aswathy Mary
George, Bijesh
Saini, Sunil
Pillai, Madhavan Radhakrishna
Toi, Masakazu
Costa, Luis
Kumar, Rakesh
Delineation of Pathogenomic Insights of Breast Cancer in Young Women
title Delineation of Pathogenomic Insights of Breast Cancer in Young Women
title_full Delineation of Pathogenomic Insights of Breast Cancer in Young Women
title_fullStr Delineation of Pathogenomic Insights of Breast Cancer in Young Women
title_full_unstemmed Delineation of Pathogenomic Insights of Breast Cancer in Young Women
title_short Delineation of Pathogenomic Insights of Breast Cancer in Young Women
title_sort delineation of pathogenomic insights of breast cancer in young women
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221490/
https://www.ncbi.nlm.nih.gov/pubmed/35741056
http://dx.doi.org/10.3390/cells11121927
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