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A novel panel of proteins correlating with lymph node metastasis of low-grade breast cancer as identified by combined proteomics and transcriptomics approach

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BOUCHAL Pavel DVOŘÁKOVÁ Monika ROUMELIOTIS Theodoros BORTLÍČEK Zbyněk IHNATOVÁ Ivana STRUHÁROVÁ Iva BUDINSKÁ Eva GARBIS Spiros D. VOJTĚŠEK Bořivoj NENUTIL Rudolf

Rok publikování 2014
Druh Konferenční abstrakty
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Popis Introduction and objectives Current prognostic factors are not sufficient for precise risk discrimination in all groups of breast cancer patients. This is evident in the case of low grade breast tumors the small percentage of which, in disagreement with favorable prognosis, forms early lymph node metastasis. New molecular targets and biomarkers of this phenomenon are thus of high clinical need. Material and Methods We focused on identification of low grade specific, metastasis correlating proteins in the set of 48 small (T1) grade 1 luminal A primary breast tumors. Another set of 48 high grade tumors of various subtypes was analyzed to investigate the specificity of identified gene products. 4405 proteins were identified (FDR < 5%) within iTRAQ-2DLC-MS/MS proteomics analysis. Expression of 95 selected genes was analyzed at transcript level. Levels of top 5 proteins were analyzed also using immunohistochemistry. Connection of gene expression and patient survival was investigated in completely independent set of 214 breast tumors. Results and Discussion The panel of identified proteins correlating with lymph node positivity low grade breast tumors at protein and transcript level, supported by similar trends in immunohistochemistry and patient survival data, involved activators of NF-?B pathway, secreted protease and cytoskeletal proteins. Analysis of biomarker selectivity divided the potential biomarkers into two selectivity groups: (i) Gene products up-regulated specifically in lymph node positive low grade tumors, (ii) those that had, in addition, higher levels in another groups of aggressive tumors (high grade and triple negative breast cancer). Conclusions The group of identified functionally relevant biomarkers in now in the process of further validation and deeper characterization of their role in breast cancer metastasis.
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