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Quantitative proteome profiling of human myoma and myometrium tissue reveals kinase expression signatures with potential for therapeutic intervention
Author(s) -
Lemeer Simone,
Gholami Amin Moghaddas,
Wu Zhixiang,
Kuster Bernhard
Publication year - 2015
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201400213
Subject(s) - kinase , biology , ddr1 , proteome , myometrium , extracellular matrix , receptor tyrosine kinase , myoma , tyrosine kinase , signal transduction , microbiology and biotechnology , leiomyoma , cancer research , bioinformatics , computational biology , pathology , medicine , genetics , uterus
Uterine leiomyomas are benign tumors affecting a large proportion of the female population. Despite the very high prevalence, the molecular basis for understanding the onset and development of the disease are still poorly understood. In this study, we profiled the proteomes and kinomes of leiomyoma as well as myometrium samples from patients to a depth of >7000 proteins including 200 kinases. Statistical analysis identified a number of molecular signatures distinguishing healthy from diseased tissue. Among these, nine kinases (ADCK4, CDK5, CSNK2B, DDR1, EPHB1, MAP2K2, PRKCB, PRKG1, and RPS6KA5) representing a number of cellular signaling pathways showed particularly strong discrimination potential. Preliminary statistical analysis by receiver operator characteristics plots revealed very good performance for individual kinases (area under the curve, AUC of 0.70–0.94) as well as binary combinations thereof (AUC 0.70–1.00) that might be used to assess the activity of signaling pathways in myomas. Of note, the receptor tyrosine kinase DDR1 holds future potential as a drug target owing to its strong links to collagen signaling and the excessive formation of extracellular matrix typical for leiomyomas in humans.