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Identification of TUBB2A by quantitative proteomic analysis as a novel biomarker for the prediction of distant metastatic breast cancer

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Authors
Shin, Dongyoon; Park, Joonho; Han, Dohyun; Moon, Ji Hye; Ryu, Han Suk; Kim, Youngsoo
Issue Date
2020-05-24
Publisher
BMC
Citation
Clinical Proteomics. 2020 May 24;17(1):16
Keywords
Distant metastatic breast cancerFormalin-fxed parafn-embedded (FFPE) tissueBiomarkersTandem mass tag (TMT)Quantitative proteomics
Abstract
Background
Metastasis of breast cancer to distal organs is fatal. However, few studies have identified biomarkers that are associated with distant metastatic breast cancer. Furthermore, the inability of current biomarkers, such as HER2, ER, and PR, to differentiate between distant and nondistant metastatic breast cancers accurately has necessitated the development of novel biomarker candidates.

Methods
An integrated proteomics approach that combined filter-aided sample preparation, tandem mass tag labeling (TMT), high pH fractionation, and high-resolution MS was applied to acquire in-depth proteomic data from FFPE distant metastatic breast cancer tissues. A bioinformatics analysis was performed with regard to gene ontology and signaling pathways using differentially expressed proteins (DEPs) to examine the molecular characteristics of distant metastatic breast cancer. In addition, real-time polymerase chain reaction (RT-PCR) and invasion/migration assays were performed to validate the differential regulation and function of our protein targets.

Results
A total of 9441 and 8746 proteins were identified from the pooled and individual sample sets, respectively. Based on our criteria, TUBB2A was selected as a novel biomarker candidate. The metastatic activities of TUBB2A were subsequently validated. In our bioinformatics analysis using DEPs, we characterized the overall molecular features of distant metastasis and measured differences in the molecular functions of distant metastatic breast cancer between breast cancer subtypes.

Conclusions
Our report is the first study to examine the distant metastatic breast cancer proteome using FFPE tissues. The depth of our dataset allowed us to discover a novel biomarker candidate and a proteomic characteristics of distant metastatic breast cancer. Distinct molecular features of various breast cancer subtypes were also established. Our proteomic data constitute a valuable resource for research on distant metastatic breast cancer.
ISSN
1559-0275
Language
English
URI
https://doi.org/10.1186/s12014-020-09280-z

http://hdl.handle.net/10371/168571
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Journal Papers (저널논문_의과학과)
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