title: Ephrin-B2 overexpression predicts for poor prognosis and response to therapy in solid tumors.
abstract: Ephrin B2 is variably expressed on tumor cells and its blockade has been shown to inhibit angiogenesis in animal models of pancreatic, colorectal, lung and head, and neck squamous cell carcinomas. However, the implications of ephrinB2 expression in cancer patients have remained elusive. In this study, we analyzed the cancer genome atlas (TCGA) for ephrinB2 expression. We report significant correlations between EFNB2 expression, overall survival and disease-free survival in head and neck squamous cell carcinoma (HNSCC, n = 519), pancreatic adenocarcinoma (n = 186), and bladder urothelial carcinoma (n = 410). In HNSCC patients, high-EFNB2 mRNA expression was associated with tumor HPV negativity, oral cavity location, alcohol intake, higher TP53 mutation, and EGFR amplification. EphrinB2 overexpression also correlated with worse response to chemotherapy and radiotherapy. The therapeutic potential of blocking ephrinB2 was validated in HNSCC patient-derived tumor xenografts and showed significant improvement in survival and tumor growth delay. Our data shows that ephrinB2 overexpression can serve as a critical biomarker for patient prognosis and response to therapy. These results should guide design of future clinical trials exploring EphrinB2 inhibition in cancer patients. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Radiation Oncology, Anschutz Medical Campus, University of Colorado Denver, Denver, Colorado.
authors.forename: Ayman
authors.initials: A
authors.lastname: Oweida
authors.affiliation: Department of Radiation Oncology, Anschutz Medical Campus, University of Colorado Denver, Denver, Colorado.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: Department of Radiation Oncology, Anschutz Medical Campus, University of Colorado Denver, Denver, Colorado.
authors.forename: Kellen
authors.initials: K
authors.lastname: Hirsch
authors.affiliation: Department of Radiation Oncology, Anschutz Medical Campus, University of Colorado Denver, Denver, Colorado.
authors.forename: Dylan
authors.initials: D
authors.lastname: Calame
authors.affiliation: Department of Radiation Oncology, Anschutz Medical Campus, University of Colorado Denver, Denver, Colorado.
authors.forename: Anastacia
authors.initials: A
authors.lastname: Griego
authors.affiliation: Department of Oncology, Anschutz Medical Campus, University of Colorado Denver, Denver, Colorado.
authors.forename: Steve
authors.initials: S
authors.lastname: Keysar
authors.affiliation: Division of Medical Oncology, Anschutz Medical Campus, University of Colorado Denver, Denver, Colorado.
authors.forename: Todd
authors.initials: T
authors.lastname: Pitts
authors.affiliation: Department of Radiation Oncology, Anschutz Medical Campus, University of Colorado Denver, Denver, Colorado.
authors.forename: Jaspreet
authors.initials: J
authors.lastname: Sharma
authors.affiliation: Division of Medical Oncology, Anschutz Medical Campus, University of Colorado Denver, Denver, Colorado.
authors.forename: Gail
authors.initials: G
authors.lastname: Eckhardt
authors.affiliation: Department of Oncology, Anschutz Medical Campus, University of Colorado Denver, Denver, Colorado.
authors.forename: Antonio
authors.initials: A
authors.lastname: Jimeno
authors.affiliation: Department of Pathology, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado.
authors.forename: Xiao Jing
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Vasgene Therapeutics, Los Angeles, California.|Department of Oncology, University of Southern California, Los Angeles, Southern California.
authors.forename: Gill
authors.initials: G
authors.lastname: Parkash
authors.affiliation: Department of Otolaryngology, University of Southern California, San Diego, Southern California.
authors.forename: Joseph
authors.initials: J
authors.lastname: Califano
authors.affiliation: Department of Radiation Oncology, Anschutz Medical Campus, University of Colorado Denver, Denver, Colorado.
authors.forename: Sana D
authors.initials: SD
authors.lastname: Karam
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D036388:Ephrin-B2 / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C000601239:EFNB2 protein, human; D036388:Ephrin-B2
keywords: cancer; chemotherapy; ephrin; radiation therapy