A Set of miRNAs, Their Gene and Protein Targets and Stromal Genes Distinguish Early from Late Onset ER Positive Breast Cancer.
UNLABELLED:Breast cancer (BC) in young adult patients (YA) has a more aggressive biological behavior and is associated with a worse prognosis than BC arising in middle aged patients (MA). We proposed that differentially expressed miRNAs could regulate genes and proteins underlying aggressive phenoty...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4859528?pdf=render |
| _version_ | 1818838813305208832 |
|---|---|
| author | E P Bastos H Brentani C A B Pereira A Polpo L Lima R D Puga F S Pasini C A B T Osorio R A Roela M I Achatz A P Trapé A M Gonzalez-Angulo M M Brentani |
| author_facet | E P Bastos H Brentani C A B Pereira A Polpo L Lima R D Puga F S Pasini C A B T Osorio R A Roela M I Achatz A P Trapé A M Gonzalez-Angulo M M Brentani |
| author_sort | E P Bastos |
| collection | DOAJ |
| description | UNLABELLED:Breast cancer (BC) in young adult patients (YA) has a more aggressive biological behavior and is associated with a worse prognosis than BC arising in middle aged patients (MA). We proposed that differentially expressed miRNAs could regulate genes and proteins underlying aggressive phenotypes of breast tumors in YA patients when compared to those arising in MA patients. OBJECTIVE:Using integrated expression analyses of miRs, their mRNA and protein targets and stromal gene expression, we aimed to identify differentially expressed profiles between tumors from YA-BC and MA-BC. METHODOLOGY AND RESULTS:Samples of ER+ invasive ductal breast carcinomas, divided into two groups: YA-BC (35 years or less) or MA-BC (50-65 years) were evaluated. Screening for BRCA1/2 status according to the BOADICEA program indicated low risk of patients being carriers of these mutations. Aggressive characteristics were more evident in YA-BC versus MA-BC. Performing qPCR, we identified eight miRs differentially expressed (miR-9, 18b, 33b, 106a, 106b, 210, 518a-3p and miR-372) between YA-BC and MA-BC tumors with high confidence statement, which were associated with aggressive clinicopathological characteristics. The expression profiles by microarray identified 602 predicted target genes associated to proliferation, cell cycle and development biological functions. Performing RPPA, 24 target proteins differed between both groups and 21 were interconnected within a network protein-protein interactions associated with proliferation, development and metabolism pathways over represented in YA-BC. Combination of eight mRNA targets or the combination of eight target proteins defined indicators able to classify individual samples into YA-BC or MA-BC groups. Fibroblast-enriched stroma expression profile analysis resulted in 308 stromal genes differentially expressed between YA-BC and MA-BC. CONCLUSION:We defined a set of differentially expressed miRNAs, their mRNAs and protein targets and stromal genes that distinguish early onset from late onset ER positive breast cancers which may be involved with tumor aggressiveness of YA-BC. |
| first_indexed | 2024-12-19T03:44:21Z |
| format | Article |
| id | doaj.art-de1f223a2afd4ac4a2552b0748e14172 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T03:44:21Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-de1f223a2afd4ac4a2552b0748e141722022-12-21T20:37:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01115e015432510.1371/journal.pone.0154325A Set of miRNAs, Their Gene and Protein Targets and Stromal Genes Distinguish Early from Late Onset ER Positive Breast Cancer.E P BastosH BrentaniC A B PereiraA PolpoL LimaR D PugaF S PasiniC A B T OsorioR A RoelaM I AchatzA P TrapéA M Gonzalez-AnguloM M BrentaniUNLABELLED:Breast cancer (BC) in young adult patients (YA) has a more aggressive biological behavior and is associated with a worse prognosis than BC arising in middle aged patients (MA). We proposed that differentially expressed miRNAs could regulate genes and proteins underlying aggressive phenotypes of breast tumors in YA patients when compared to those arising in MA patients. OBJECTIVE:Using integrated expression analyses of miRs, their mRNA and protein targets and stromal gene expression, we aimed to identify differentially expressed profiles between tumors from YA-BC and MA-BC. METHODOLOGY AND RESULTS:Samples of ER+ invasive ductal breast carcinomas, divided into two groups: YA-BC (35 years or less) or MA-BC (50-65 years) were evaluated. Screening for BRCA1/2 status according to the BOADICEA program indicated low risk of patients being carriers of these mutations. Aggressive characteristics were more evident in YA-BC versus MA-BC. Performing qPCR, we identified eight miRs differentially expressed (miR-9, 18b, 33b, 106a, 106b, 210, 518a-3p and miR-372) between YA-BC and MA-BC tumors with high confidence statement, which were associated with aggressive clinicopathological characteristics. The expression profiles by microarray identified 602 predicted target genes associated to proliferation, cell cycle and development biological functions. Performing RPPA, 24 target proteins differed between both groups and 21 were interconnected within a network protein-protein interactions associated with proliferation, development and metabolism pathways over represented in YA-BC. Combination of eight mRNA targets or the combination of eight target proteins defined indicators able to classify individual samples into YA-BC or MA-BC groups. Fibroblast-enriched stroma expression profile analysis resulted in 308 stromal genes differentially expressed between YA-BC and MA-BC. CONCLUSION:We defined a set of differentially expressed miRNAs, their mRNAs and protein targets and stromal genes that distinguish early onset from late onset ER positive breast cancers which may be involved with tumor aggressiveness of YA-BC.http://europepmc.org/articles/PMC4859528?pdf=render |
| spellingShingle | E P Bastos H Brentani C A B Pereira A Polpo L Lima R D Puga F S Pasini C A B T Osorio R A Roela M I Achatz A P Trapé A M Gonzalez-Angulo M M Brentani A Set of miRNAs, Their Gene and Protein Targets and Stromal Genes Distinguish Early from Late Onset ER Positive Breast Cancer. PLoS ONE |
| title | A Set of miRNAs, Their Gene and Protein Targets and Stromal Genes Distinguish Early from Late Onset ER Positive Breast Cancer. |
| title_full | A Set of miRNAs, Their Gene and Protein Targets and Stromal Genes Distinguish Early from Late Onset ER Positive Breast Cancer. |
| title_fullStr | A Set of miRNAs, Their Gene and Protein Targets and Stromal Genes Distinguish Early from Late Onset ER Positive Breast Cancer. |
| title_full_unstemmed | A Set of miRNAs, Their Gene and Protein Targets and Stromal Genes Distinguish Early from Late Onset ER Positive Breast Cancer. |
| title_short | A Set of miRNAs, Their Gene and Protein Targets and Stromal Genes Distinguish Early from Late Onset ER Positive Breast Cancer. |
| title_sort | set of mirnas their gene and protein targets and stromal genes distinguish early from late onset er positive breast cancer |
| url | http://europepmc.org/articles/PMC4859528?pdf=render |
| work_keys_str_mv | AT epbastos asetofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT hbrentani asetofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT cabpereira asetofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT apolpo asetofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT llima asetofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT rdpuga asetofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT fspasini asetofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT cabtosorio asetofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT raroela asetofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT miachatz asetofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT aptrape asetofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT amgonzalezangulo asetofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT mmbrentani asetofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT epbastos setofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT hbrentani setofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT cabpereira setofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT apolpo setofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT llima setofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT rdpuga setofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT fspasini setofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT cabtosorio setofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT raroela setofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT miachatz setofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT aptrape setofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT amgonzalezangulo setofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer AT mmbrentani setofmirnastheirgeneandproteintargetsandstromalgenesdistinguishearlyfromlateonseterpositivebreastcancer |