title: Identification of receptor tyrosine kinase, discoidin domain receptor 1 (DDR1), as a potential biomarker for serous ovarian cancer.
abstract: Ovarian cancer, one of the most common gynecological malignancies, has an aggressive phenotype. It is necessary to develop novel and more effective treatment strategies against advanced disease. Protein tyrosine kinases (PTKs) play an important role in the signal transduction pathways involved in tumorigenesis, and represent potential targets for anticancer therapies. In this study, we performed cDNA subtraction following polymerase chain reaction (PCR) using degenerate oligonucleotide primers to identify specifically overexpressed PTKs in ovarian cancer. Three PTKs, janus kinase 1, insulin-like growth factor 1 receptor, and discoidin domain receptor 1 (DDR1), were identified and only DDR1 was overexpressed in all ovarian cancer tissues examined for the validation by quantitative real-time PCR. The DDR1 protein was expressed in 63% (42/67) of serous ovarian cancer tissue, whereas it was undetectable in normal ovarian surface epithelium. DDR1 was expressed significantly more frequently in high-grade (79%) and advanced stage (77%) tumors compared to low-grade (50%) and early stage (43%) tumors. The expression of the DDR1 protein significantly correlated with poor disease-free survival. Although its functional role and clinical utility remain to be examined in future studies, our results suggest that the expression of DDR1 may serve as both a potential biomarker and a molecular target for advanced ovarian cancer.
authors.affiliation: Division of Obstetrics and Gynecology, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, 951-8520, Japan; E-Mails: zenkinka@yahoo.co.jp (J.Q.); sadachi@med.niigata-u.ac.jp (S.A.); yoshikou@med.niigata-u.ac.jp (K.Y.); tanaken@med.niigata-u.ac.jp (K.T.).
authors.forename: Jinhua
authors.initials: J
authors.lastname: Quan
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yahata
authors.forename: Sosuke
authors.initials: S
authors.lastname: Adachi
authors.forename: Kosuke
authors.initials: K
authors.lastname: Yoshihara
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D003537:Cystadenoma / Q000175:diagnosis* / Q000378:metabolism; D000070819:Discoidin Domain Receptor 1; D005260:Female; D006801:Humans; D053613:Janus Kinase 1 / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D012704:Serous Membrane / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C092030:DDR1 protein, human; D000070819:Discoidin Domain Receptor 1; D020794:Receptor Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; C507904:JAK1 protein, human; D053613:Janus Kinase 1