Combined Proteomics and Transcriptomics Identifies
Carboxypeptidase B1 and Nuclear Factor kappa B (NF-kappa B)
Associated Proteins as Putative Biomarkers of Metastasis in Low
Grade Breast Cancer

J 2015

Combined Proteomics and Transcriptomics Identifies Carboxypeptidase B1 and Nuclear Factor kappa B (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 Nuclear Factor kappa B (NF-kappa B) Associated Proteins as Putative Biomarkers of Metastasis in Low Grade Breast Cancer

Authors

BOUCHAL, Pavel (203 Czech Republic, belonging to the institution), Monika DVOŘÁKOVÁ (203 Czech Republic, belonging to the institution), Theodoros ROUMELIOTIS (300 Greece), Zbyněk BORTLÍČEK (203 Czech Republic, belonging to the institution), Ivana IHNATOVÁ (703 Slovakia, belonging to the institution), Iva PROCHÁZKOVÁ (203 Czech Republic), JTC HO (826 United Kingdom of Great Britain and Northern Ireland), Josef MARYÁŠ (203 Czech Republic, belonging to the institution), Hana IMRICHOVÁ (203 Czech Republic), Eva BUDINSKÁ (703 Slovakia, belonging to the institution), Rostislav VYZULA (203 Czech Republic), SD GARBIS (300 Greece), Bořivoj VOJTĚŠEK (203 Czech Republic) and Rudolf NENUTIL (203 Czech Republic)

Edition

MOLECULAR & CELLULAR PROTEOMICS, BETHESDA, AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2015, 1535-9476

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 5.912

RIV identification code

RIV/00216224:14310/15:00080960

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1074/mcp.M114.041335

UT WoS

000357434400007

Keywords in English

Breast cancer; metastasis; low grade; biomarkers; cancer biology; gene expression; iTRAQ; mass spectrometry; Orbitrap FTMS; transcriptomics; Carboxypeptidase B1; NFkB

Abstract

V originále

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. 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. 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 (versus negative) luminal A tumors was validated by gene expression analysis of an independent published data set (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 data set (n = 1678). Our findings indicate unique pro-metastatic mechanisms in grade 1 tumors that can include up-regulation of CPB1, activation of NF-kappa B pathway and changes in cell survival and cytoskeleton. These putative biomarkers have potential to identify the specific minor subpopulation of breast cancer patients with low grade tumors who are at higher than expected risk of recurrence.

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, SD GARBIS, Bořivoj VOJTĚŠEK and Rudolf NENUTIL. Combined Proteomics and Transcriptomics Identifies Carboxypeptidase B1 and Nuclear Factor kappa B (NF-kappa B) Associated Proteins as Putative Biomarkers of Metastasis in Low Grade Breast Cancer. MOLECULAR & CELLULAR PROTEOMICS. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2015, vol. 14, No 7, p. 1814-1830. ISSN 1535-9476. Available from: https://dx.doi.org/10.1074/mcp.M114.041335.

@article{1308775,
   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, SD and Vojtěšek, Bořivoj and Nenutil, Rudolf},
   article_location = {BETHESDA},
   article_number = {7},
   doi = {http://dx.doi.org/10.1074/mcp.M114.041335},
   keywords = {Breast cancer; metastasis; low grade; biomarkers; cancer biology; gene expression; iTRAQ; mass spectrometry; Orbitrap FTMS; transcriptomics; Carboxypeptidase B1; NFkB},
   language = {eng},
   issn = {1535-9476},
   journal = {MOLECULAR & CELLULAR PROTEOMICS},
   title = {Combined Proteomics and Transcriptomics Identifies Carboxypeptidase B1 and Nuclear Factor kappa B (NF-kappa B) Associated Proteins as Putative Biomarkers of Metastasis in Low Grade Breast Cancer},
   volume = {14},
   year = {2015}
}

TY  - JOUR
ID  - 1308775
AU  - Bouchal, Pavel - Dvořáková, Monika - Roumeliotis, Theodoros - Bortlíček, Zbyněk - Ihnatová, Ivana - Procházková, Iva - Ho, JTC - Maryáš, Josef - Imrichová, Hana - Budinská, Eva - Vyzula, Rostislav - Garbis, SD - Vojtěšek, Bořivoj - Nenutil, Rudolf
PY  - 2015
TI  - Combined Proteomics and Transcriptomics Identifies Carboxypeptidase B1 and Nuclear Factor kappa B (NF-kappa B) Associated Proteins as Putative Biomarkers of Metastasis in Low Grade Breast Cancer
JF  - MOLECULAR & CELLULAR PROTEOMICS
VL  - 14
IS  - 7
SP  - 1814-1830
EP  - 1814-1830
PB  - AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
SN  - 15359476
KW  - Breast cancer
KW  - metastasis
KW  - low grade
KW  - biomarkers
KW  - cancer biology
KW  - gene expression
KW  - iTRAQ
KW  - mass spectrometry
KW  - Orbitrap FTMS
KW  - transcriptomics
KW  - Carboxypeptidase B1
KW  - NFkB
N2  - 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. 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. 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 (versus negative) luminal A tumors was validated by gene expression analysis of an independent published data set (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 data set (n = 1678). Our findings indicate unique pro-metastatic mechanisms in grade 1 tumors that can include up-regulation of CPB1, activation of NF-kappa B pathway and changes in cell survival and cytoskeleton. These putative biomarkers have potential to identify the specific minor subpopulation of breast cancer patients with low grade tumors who are at higher than expected risk of recurrence.
ER  -

BOUCHAL, Pavel, Monika DVOŘÁKOVÁ, Theodoros ROUMELIOTIS, Zbyněk BORTLÍČEK, Ivana IHNATOVÁ, Iva PROCHÁZKOVÁ, JTC HO, Josef MARYÁŠ, Hana IMRICHOVÁ, Eva BUDINSKÁ, Rostislav VYZULA, SD GARBIS, Bořivoj VOJTĚŠEK and Rudolf NENUTIL. Combined Proteomics and Transcriptomics Identifies Carboxypeptidase B1 and Nuclear Factor kappa B (NF-kappa B) Associated Proteins as Putative Biomarkers of Metastasis in Low Grade Breast Cancer. \textit{MOLECULAR \&{}amp; CELLULAR PROTEOMICS}. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2015, vol.~14, No~7, p.~1814-1830. ISSN~1535-9476. Available from: https://dx.doi.org/10.1074/mcp.M114.041335.

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