Publicação
Delineation of pathogenomic insights of breast cancer in young women
| Resumo: | 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. |
|---|---|
| Autores principais: | Paul, Aswathy Mary |
| Outros Autores: | George, Bijesh; Saini, Sunil; Pillai, Madhavan Radhakrishna; Toi, Masakazu; Costa, Luis; Kumar, Rakesh |
| Assunto: | Early breast cancer Genomics Predictive biomarkers Prognosis Transcriptomics Young women |
| Ano: | 2022 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| _version_ | 1866811177047162880 |
|---|---|
| author | Paul, Aswathy Mary |
| author2 | George, Bijesh Saini, Sunil Pillai, Madhavan Radhakrishna Toi, Masakazu Costa, Luis Kumar, Rakesh |
| author2_role | author author author author author author |
| author_facet | Paul, Aswathy Mary George, Bijesh Saini, Sunil Pillai, Madhavan Radhakrishna Toi, Masakazu Costa, Luis Kumar, Rakesh |
| author_role | author |
| contributor_name_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Paul, Aswathy Mary\"},{\"Person.name\":\"George, Bijesh\"},{\"Person.name\":\"Saini, Sunil\"},{\"Person.name\":\"Pillai, Madhavan Radhakrishna\"},{\"Person.name\":\"Toi, Masakazu\"},{\"Person.name\":\"Costa, Luis\",\"Person.identifier.orcid\":\"0000-0002-4782-7318\"},{\"Person.name\":\"Kumar, Rakesh\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| datacite.creators.creator.creatorName.fl_str_mv | Paul, Aswathy Mary George, Bijesh Saini, Sunil Pillai, Madhavan Radhakrishna Toi, Masakazu Costa, Luis Kumar, Rakesh |
| datacite.date.Accepted.fl_str_mv | 2022-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2022-07-18T16:29:17Z |
| datacite.date.embargoed.fl_str_mv | 2022-07-18T16:29:17Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Early breast cancer Genomics Predictive biomarkers Prognosis Transcriptomics Young women |
| datacite.titles.title.fl_str_mv | Delineation of pathogenomic insights of breast cancer in young women |
| dc.contributor.none.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| dc.creator.none.fl_str_mv | Paul, Aswathy Mary George, Bijesh Saini, Sunil Pillai, Madhavan Radhakrishna Toi, Masakazu Costa, Luis Kumar, Rakesh |
| dc.date.Accepted.fl_str_mv | 2022-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2022-07-18T16:29:17Z |
| dc.date.embargoed.fl_str_mv | 2022-07-18T16:29:17Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10451/53844 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | MDPI |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Early breast cancer Genomics Predictive biomarkers Prognosis Transcriptomics Young women |
| dc.title.fl_str_mv | Delineation of pathogenomic insights of breast cancer in young women |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ulisboa.pt/bitstreams/f00708a9-11b6-4bab-9769-6cfebbc592d6/download |
| id | ul_632f827dfdb63c0a4c194487ea843c1a |
| identifier.url.fl_str_mv | http://hdl.handle.net/10451/53844 |
| instacron_str | ul |
| institution | Universidade de Lisboa |
| instname_str | Universidade de Lisboa |
| language | eng |
| network_acronym_str | ul |
| network_name_str | Repositório da Universidade de Lisboa |
| oai_identifier_str | oai:repositorio.ulisboa.pt:10451/53844 |
| organization_str_mv | urn:organizationAcronym:ul |
| person_str_mv | Paul, Aswathy Mary George, Bijesh Saini, Sunil Pillai, Madhavan Radhakrishna Toi, Masakazu Costa, Luis Costa, Luis https://www.ciencia-id.pt/041E-4ADE-FB64 041E-4ADE-FB64 http://orcid.org/0000-0002-4782-7318 0000-0002-4782-7318 Kumar, Rakesh |
| publishDate | 2022 |
| publisher.none.fl_str_mv | MDPI |
| reponame_str | Repositório da Universidade de Lisboa |
| repository_id_str | urn:repositoryAcronym:ul |
| service_str_mv | urn:repositoryAcronym:ul |
| spelling | engMDPIpt_PTThe 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.application/pdfpt_PTDelineation of pathogenomic insights of breast cancer in young womenPaul, Aswathy MaryGeorge, BijeshSaini, SunilPillai, Madhavan RadhakrishnaToi, MasakazuPersonalCosta, LuisDSpacehttp://dspace.org/items/8a2ab4c6-ba86-4433-b4b7-6256d81890e5DSpacehttp://dspace.org/items/8a2ab4c6-ba86-4433-b4b7-6256d81890e5CostaLuisCiência IDhttps://www.ciencia-id.pt041E-4ADE-FB64ORCIDhttp://orcid.org0000-0002-4782-7318Kumar, RakeshHostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptDOIIsPartOf10.3390/cells111219272022-07-18T16:29:17Z20222022-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/53844http://purl.org/coar/access_right/c_abf2open accessEarly breast cancerGenomicsPredictive biomarkersPrognosisTranscriptomicsYoung women11471923 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal article2022http://creativecommons.org/licenses/by/4.0/http://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/f00708a9-11b6-4bab-9769-6cfebbc592d6/downloadCells1112 |
| spellingShingle | Delineation of pathogenomic insights of breast cancer in young women Paul, Aswathy Mary Early breast cancer Genomics Predictive biomarkers Prognosis Transcriptomics Young women |
| status | SINGLETON |
| subject.fl_str_mv | Early breast cancer Genomics Predictive biomarkers Prognosis Transcriptomics 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 | Early breast cancer Genomics Predictive biomarkers Prognosis Transcriptomics Young women |
| topic_facet | Early breast cancer Genomics Predictive biomarkers Prognosis Transcriptomics Young women |
| url | http://hdl.handle.net/10451/53844 |
| visible | 1 |