title: Increased expression of discoidin domain receptor 2 (DDR2): a novel independent prognostic marker of worse outcome in breast cancer patients.
abstract: The discoidin domain receptors, DDR1 and DDR2, have been linked with numerous human cancers. We sought to determine expression level and distribution of DDRs in human breast cancer, and investigate prognostic determinates to determine whether levels of DDRs could predict survival. Tumor samples from 122 breast cancer patients were analyzed for relative expression of DDRs. An additional 24 matched tumor and normal tissues were tested for differential expression of DDR1 and DDR2. DDR2 was found to be significantly increased by 6-fold (P = 0.0005) and DDR1 decreased (P = 0.0001) in tumor vs. normal breast tissue. DDR1 expression was not predictive for patient survival; however, DDR2 expression was significantly associated with disease-free (HR = 0.55, 95 % CI = 0.24-0.78, P = 0.026) and overall survival (HR = 0.46, 95 % CI = 0.35-0.84, P = 0.019). Multivariate analysis revealed DDR2 is an independent favorable predictor for prognosis independent of tumor stage, histology, and patient age. The present research provided the first evidence that increased DDR2 mRNA expression in primary human breast cancer might be a powerful, independent predictor of recurrence and outcome.
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Changle Western Road, Xi'an, Shaanxi 710032, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Ren
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Xinping
authors.initials: X
authors.lastname: Liu
authors.forename: Libo
authors.initials: L
authors.lastname: Yao
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000070819:Discoidin Domain Receptor 1; D000070818:Discoidin Domain Receptors; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D011975:Receptors, Mitogen / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D011975:Receptors, Mitogen; C092030:DDR1 protein, human; D000070819:Discoidin Domain Receptor 1; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases