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

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.

Basic information

Original name

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

Authors

Edition

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

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

10600 1.6 Biological sciences

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 6.163

Organization unit

Faculty of Science

ISSN

Keywords in English

proteomics; breast cancer

Abstract

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.

Links

GA14-19250S, research and development project

Name: Nový panel proteinů korelujících se stavem lymfatických uzlin u low-grade nádorů prsu: Klinická verifikace a úloha v invazivitě nádorových buněk

Investor: Czech Science Foundation

Citovat

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 and Rudolf NENUTIL. Combined proteomics and transcriptomics identifies carboxypeptidase B1 and NF-kappa B associated proteins as putative biomarkers of metastasis in low grade breast cancer. In 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. ISSN 0959-8049.

@proceedings{1351782,
   author = {Bouchal, Pavel and Dvořáková, Monika and Roumeliotis, Theodoros and Bortlíček, Zbyněk and Ihnatová, Ivana and Procházková, Iva and Ho, JTC and Maryáš, Josef and Imrichová, Hana and Budinská, Eva and Vyzula, Rostislav and Garbis, Spiros D, and Vojtěšek, Bořivoj and Nenutil, Rudolf},
   booktitle = {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.},
   keywords = {proteomics; breast cancer},
   language = {eng},
   title = {Combined proteomics and transcriptomics identifies carboxypeptidase B1 and NF-kappa B associated proteins as putative biomarkers of metastasis in low grade breast cancer},
   year = {2015}
}

TY  - CONF
ID  - 1351782
AU  - Bouchal, Pavel - Dvořáková, Monika - Roumeliotis, Theodoros - Bortlíček, Zbyněk - Ihnatová, Ivana - Procházková, Iva - Ho, JTC - Maryáš, Josef - Imrichová, Hana - Budinská, Eva - Vyzula, Rostislav - Garbis, Spiros D, - Vojtěšek, Bořivoj - Nenutil, Rudolf
PY  - 2015
TI  - Combined proteomics and transcriptomics identifies carboxypeptidase B1 and NF-kappa B associated proteins as putative biomarkers of metastasis in low grade breast cancer
KW  - proteomics
KW  - breast cancer
N2  - 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.
ER  -

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 and Rudolf NENUTIL. Combined proteomics and transcriptomics identifies carboxypeptidase B1 and NF-kappa B associated proteins as putative biomarkers of metastasis in low grade breast cancer. In \textit{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. ISSN~0959-8049.

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