PXD000029-4
PXD000029 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Combined proteomics and transcriptomics identifies carboxypeptidase B1 and NF-κB associated proteins as putative biomarkers of metastasis in low grade breast cancer |
Description | 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 (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). Our findings indicate unique pro-metastatic mechanisms in grade 1 tumors that can include up-regulation of CPB1, activation of NF-κB 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 than expected risk of recurrence and who would benefit from more intensive follow-up and may require more personalized therapy. |
HostingRepository | PRIDE |
AnnounceDate | 2017-10-24 |
AnnouncementXML | Submission_2017-10-24_00:15:19.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Pavel Bouchal |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | methylthiolated residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2012-09-18 08:23:18 | ID requested | |
1 | 2015-04-23 07:46:34 | announced | |
2 | 2015-07-16 02:55:16 | announced | Updated publication reference for PubMed record(s): 25903579. |
3 | 2017-06-21 00:30:57 | announced | Updated project metadata. |
⏵ 4 | 2017-10-24 00:15:20 | announced | Updated project metadata. |
Publication List
Bouchal P, Dvo, ř, á, kov, á M, Roumeliotis T, Bortl, í, č, ek Z, Ihnatov, á I, Proch, á, zkov, á I, Ho JT, Mary, á, š J, Imrichov, á H, Budinsk, á E, Vyzula R, Garbis SD, Vojt, ě, š, ek B, Nenutil R, B) Associated Proteins as Putative Biomarkers of Metastasis in Low Grade Breast Cancer. Mol Cell Proteomics, 14(7):1814-30(2015) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: Breast cancer, metastasis, low grade, biomarkers, cancer biology, gene expression, iTRAQ, mass spectrometry, Orbitrap FTMS, transcriptomics, Carboxypeptidase-B1, NF-B |
Contact List
Pavel Bouchal | |
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contact affiliation | Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology and Masaryk University, Faculty of Science, Brno, Czech Republic |
contact email | bouchal@chemi.muni.cz |
lab head | |
Pavel Bouchal | |
contact affiliation | Masaryk University & Masaryk Memorial Cancer Institute, Brno, Czech Republic |
contact email | bouchal@chemi.muni.cz |
dataset submitter |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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