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Breast Cancer Classification Based on Proteotypes Obtained by SWATH Mass Spectrometry

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BOUCHAL Pavel SCHUBERT Olga T. FAKTOR Jakub ČÁPKOVÁ Lenka IMRICHOVÁ Hana ZOUFALOVÁ Karolína PÁRALOVÁ Vendula HRSTKA Roman LIU Yansheng S. EBHARDT Holger A. BUDINSKÁ Eva NENUTIL Rudolf AEBERSOLD Ruedi

Druh Článek v odborném periodiku
Časopis / Zdroj Cell Reports
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Doi http://dx.doi.org/10.1016/j.celrep.2019.06.046
Klíčová slova SWATH-MS; breast cancer; data independent acquisition; proteomics; tissue; transcriptomics; tumor classification
Popis Accurate classification of breast tumors is vital for patient management decisions and enables more precise cancer treatment. Here, we present a quantitative proteotyping approach based on sequential windowed acquisition of all theoretical fragment ion spectra (SWATH) mass spectrometry and establish key proteins for breast tumor classification. The study is based on 96 tissue samples representing five conventional breast cancer subtypes. SWATH proteotype patterns largely recapitulate these subtypes; however, they also reveal varying heterogeneity within the conventional subtypes, with triple negative tumors being the most heterogeneous. Proteins that contribute most strongly to the proteotype-based classification include INPP4B, CDK1, and ERBB2 and are associated with estrogen receptor (ER) status, tumor grade status, and HER2 status. Although these three key proteins exhibit high levels of correlation with transcript levels (R > 0.67), general correlation did not exceed R = 0.29, indicating the value of protein-level measurements of disease-regulated genes. Overall, this study highlights how cancer tissue proteotyping can lead to more accurate patient stratification.
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