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Statements

Subject Item
n2:RIV%2F61989592%3A15110%2F11%3A10225465%21RIV15-MSM-15110___
rdf:type
skos:Concept n18:Vysledek
dcterms:description
MiR-34a acts as a candidate tumour suppressor gene, and its expression is reduced in several cancer types. We aimed to study miR-34a expression in breast cancer and its correlation with tumour characteristics and clinical outcome, and regulatory links with other genes. We analysed miR-34a expression in 1,172 breast tumours on TMAs. 25% of the tumours showed high, 43% medium and 32% low expression of miR-34a. High miR-34a expression associated with poor prognostic factors for breast cancer: positive nodal status (p = 0.006), high tumour grade (p { 0.0001), ER-negativity (p = 0.0002), HER2-positivity (p = 0.0002), high proliferation rate (p { 0.0001), p53-positivity (p { 0.0001), high cyclin E (p { 0.0001) and gamma H2AX (p { 0.0001). However, multivariate analysis adjusting for conventional prognostic factors indicated that high miR-34a expression in fact associated with a lower risk of recurrence or death from breast cancer (HR = 0.63, 95% CI = 0.41-0.96, p = 0.031). Gene expression analysis by differential miR-34a expression revealed an expression signature with an effect on both the 5-year and 10-year survival of the patients (p { 0.001). Functional genomic analysis highlighted a novel regulatory role of the transcription factor MAZ, apart from the known control by p53, on the expression of miR-34a and a number of miR-34a targets. Our findings suggest that while miR-34a expression activation is a marker of aggressive breast tumour phenotype it exerts an independent effect for a lower risk of recurrence or death from breast cancer. We also present an expression signature of 190 genes associated with miR-34a expression. Our analysis for regulatory loops suggest that MAZ and p53 transcription factors co-operate in modulating miR-34a, as well as miR-34a targets involved in several cellular pathways. MiR-34a acts as a candidate tumour suppressor gene, and its expression is reduced in several cancer types. We aimed to study miR-34a expression in breast cancer and its correlation with tumour characteristics and clinical outcome, and regulatory links with other genes. We analysed miR-34a expression in 1,172 breast tumours on TMAs. 25% of the tumours showed high, 43% medium and 32% low expression of miR-34a. High miR-34a expression associated with poor prognostic factors for breast cancer: positive nodal status (p = 0.006), high tumour grade (p { 0.0001), ER-negativity (p = 0.0002), HER2-positivity (p = 0.0002), high proliferation rate (p { 0.0001), p53-positivity (p { 0.0001), high cyclin E (p { 0.0001) and gamma H2AX (p { 0.0001). However, multivariate analysis adjusting for conventional prognostic factors indicated that high miR-34a expression in fact associated with a lower risk of recurrence or death from breast cancer (HR = 0.63, 95% CI = 0.41-0.96, p = 0.031). Gene expression analysis by differential miR-34a expression revealed an expression signature with an effect on both the 5-year and 10-year survival of the patients (p { 0.001). Functional genomic analysis highlighted a novel regulatory role of the transcription factor MAZ, apart from the known control by p53, on the expression of miR-34a and a number of miR-34a targets. Our findings suggest that while miR-34a expression activation is a marker of aggressive breast tumour phenotype it exerts an independent effect for a lower risk of recurrence or death from breast cancer. We also present an expression signature of 190 genes associated with miR-34a expression. Our analysis for regulatory loops suggest that MAZ and p53 transcription factors co-operate in modulating miR-34a, as well as miR-34a targets involved in several cellular pathways.
dcterms:title
MiR-34a Expression Has an Effect for Lower Risk of Metastasis and Associates with Expression Patterns Predicting Clinical Outcome in Breast Cancer MiR-34a Expression Has an Effect for Lower Risk of Metastasis and Associates with Expression Patterns Predicting Clinical Outcome in Breast Cancer
skos:prefLabel
MiR-34a Expression Has an Effect for Lower Risk of Metastasis and Associates with Expression Patterns Predicting Clinical Outcome in Breast Cancer MiR-34a Expression Has an Effect for Lower Risk of Metastasis and Associates with Expression Patterns Predicting Clinical Outcome in Breast Cancer
skos:notation
RIV/61989592:15110/11:10225465!RIV15-MSM-15110___
n3:aktivita
n11:P n11:Z
n3:aktivity
P(ED0030/01/01), Z(MSM6198959216)
n3:cisloPeriodika
11
n3:dodaniDat
n19:2015
n3:domaciTvurceVysledku
n12:6201822
n3:druhVysledku
n13:J
n3:duvernostUdaju
n16:S
n3:entitaPredkladatele
n7:predkladatel
n3:idSjednocenehoVysledku
212673
n3:idVysledku
RIV/61989592:15110/11:10225465
n3:jazykVysledku
n6:eng
n3:klicovaSlova
MICROARRAY; BIOINFORMATICS; FAMILY; TARGET; CELLS; APOPTOSIS; MICRORNAS; GENE-EXPRESSION; DOWN-REGULATION; DNA-DAMAGE RESPONSE
n3:klicoveSlovo
n8:MICROARRAY n8:MICRORNAS n8:DNA-DAMAGE%20RESPONSE n8:DOWN-REGULATION n8:CELLS n8:TARGET n8:BIOINFORMATICS n8:GENE-EXPRESSION n8:FAMILY n8:APOPTOSIS
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[F4A0660C82E9]
n3:nazevZdroje
PLoS One
n3:obor
n15:FD
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
12
n3:projekt
n9:ED0030%2F01%2F01
n3:rokUplatneniVysledku
n19:2011
n3:svazekPeriodika
6
n3:tvurceVysledku
Bártek, Jiří Kaur, Sippy Peurala, Hanna Jamshidi, Maral Heikkinen, Tuomas Butzow, Ralf Bartková, Jiřina Heikkila, Paivi Blomqvist, Carl Nevanlinna, Heli Aittomaki, Kristiina Greco, Dario
n3:zamer
n17:MSM6198959216
s:issn
1932-6203
s:numberOfPages
10
n10:organizacniJednotka
15110