TY - JOUR
T1 - Quantitative proteome profiling of human myoma and myometrium tissue reveals kinase expression signatures with potential for therapeutic intervention
AU - Lemeer, Simone
AU - Gholami, Amin Moghaddas
AU - Wu, Zhixiang
AU - Kuster, Bernhard
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Biomedicine
KW - DDR1
KW - Label-free quantification
KW - Leiomyoma
KW - MS
UR - http://www.scopus.com/inward/record.url?scp=84921358594&partnerID=8YFLogxK
U2 - 10.1002/pmic.201400213
DO - 10.1002/pmic.201400213
M3 - Article
C2 - 25327614
AN - SCOPUS:84921358594
SN - 1615-9853
VL - 15
SP - 356
EP - 364
JO - Proteomics
JF - Proteomics
IS - 2-3
ER -