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 |
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