a 2015

Combined proteomics and transcriptomics identifies carboxypeptidase B1 and NF-kappa B associated proteins as putative biomarkers of metastasis in low grade breast cancer

BOUCHAL, Pavel, Monika DVOŘÁKOVÁ, Theodoros ROUMELIOTIS, Zbyněk BORTLÍČEK, Ivana IHNATOVÁ et. al.

Základní údaje

Originální název

Combined proteomics and transcriptomics identifies carboxypeptidase B1 and NF-kappa B associated proteins as putative biomarkers of metastasis in low grade breast cancer

Autoři

BOUCHAL, Pavel, Monika DVOŘÁKOVÁ, Theodoros ROUMELIOTIS, Zbyněk BORTLÍČEK, Ivana IHNATOVÁ, Iva PROCHÁZKOVÁ, JTC HO, Josef MARYÁŠ, Hana IMRICHOVÁ, Eva BUDINSKÁ, Rostislav VYZULA, Spiros D, GARBIS, Bořivoj VOJTĚŠEK a Rudolf NENUTIL

Vydání

European Cancer Congress 2015, Vienna, Austria, 25.-29.9.2015 - European Journal of Cancer, Vol. 51, S3. Oxford: Elsevier Science Inc., 2015. s. S24-S25, 2 s. 2015

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

10600 1.6 Biological sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 6.163

Organizační jednotka

Přírodovědecká fakulta

ISSN

Klíčová slova anglicky

proteomics; breast cancer

Příznaky

Mezinárodní význam
Změněno: 9. 1. 2019 21:20, doc. Mgr. Pavel Bouchal, Ph.D.

Anotace

V originále

Background: Current prognostic factors are insufficient for precise risk-discrimination in breast cancer patients with low grade breast tumors, which, in disagreement with theoretical prognosis, occasionally form early lymph node metastasis. Material and Methods: To identify markers for this group of patients, we employed iTRAQ-2DLC-MS/MS proteomics to 24 lymph node positive and 24 lymph node negative grade 1 luminal A primary breast tumors. Another group of 48 high-grade tumors (luminal B, triple negative, Her-2 subtypes) was also analyzed to investigate marker specificity for grade 1 luminal A tumors. Results: From the total of 4405 proteins identified (FDR<5%), the top 65 differentially expressed together with 30 previously identified and control markers were analyzed also at transcript level. Increased levels of carboxypeptidase B1 (CPB1), PDZ and LIM domain protein 2 (PDLIM2) and ring finger protein 25 (RNF25) were associated specifically with lymph node positive grade 1 tumors, whereas stathmin 1 (STMN1) and thymosin beta 10 (TMSB10) associated with aggressive tumor phenotype also in high grade tumors at both protein and transcript level. For CPB1, these differences were also observed by immunohistochemical analysis on tissue microarrays. Upregulation of putative biomarkers in lymph node positive (vs. negative) luminal A tumors was validated by gene expression analysis of an independent published dataset (N=343) for CPB1 (p=0.00155), PDLIM2 (p=0.02027) and RELA (p=0.00015). Moreover, statistically significant connections with patient survival were identified in another public dataset (N=1678). Conclusions: Our findings indicate unique pro-metastatic mechanisms in grade 1 tumors that can include up-regulation of CPB1, activation of NF-kappaB pathway and changes in cell survival and cytoskeleton. These putative biomarkers have potential to identify the specific minor sub-population of breast cancer patients with low grade tumors who are at higher risk.

Návaznosti

GA14-19250S, projekt VaV
Název: Nový panel proteinů korelujících se stavem lymfatických uzlin u low-grade nádorů prsu: Klinická verifikace a úloha v invazivitě nádorových buněk
Investor: Grantová agentura ČR, Nový panel proteinů korelujících se stavem lymfatických uzlin u low-grade nádorů prsu: Klinická verifikace a úloha v invazivitě nádorových buněk