Integrated genomics of chemotherapy resistant ovarian cancer: a role for extracellular matrix, TGFbeta and regulating microRNAs.
Epithelial ovarian cancer is the sixth most common cancer in women worldwide and the most important cause of death from gynaecological cancers in the Western world. Our explorative pathway analysis on seven published gene-sets associated with platinum resistance in ovarian cancer reveals TP53 and transforming growth factor beta as key genes. Furthermore, the extracellular matrix was associated with chemotherapy resistance in ovarian cancer as well as endocrine resistance in breast cancer. Pathway analysis again revealed transforming growth factor beta as a key gene regulating extracellular matrix gene expression. A model is presented based on literature linking transforming growth factor beta, extracellular matrix, integrin signalling, epithelial to mesenchymal transition and regulating microRNAs with a (bivalent) role in chemotherapy response.
Department of Medical Oncology, Erasmus MC/JNI, Rotterdam, The Netherlands.
Jozien
J
Helleman
Maurice P H M
MP
Jansen
Curt
C
Burger
Maria E L
ME
van der Burg
Els M J J
EM
Berns
D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005109:Extracellular Matrix / Q000235:genetics*; D005260:Female; D023281:Genomics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*
D035683:MicroRNAs; D016212:Transforming Growth Factor beta