Objectives: To examine the expression of EphB4 and EphrinB2 in tumor tissue and surrounding normal tissue in patients with head and neck squamous cell carcinoma (HNSCC) and to evaluate its association with overall patient survival.
Design: Retrospective study.
Setting: University of Southern California-University Hospital, the Los Angeles County and University of Southern California Medical Center, and the Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles.
Patients: Fifty patients, 8 with early-stage (stages I and II) and 42 with advanced-stage (stages III and IV) HNSCC, were enrolled into this study. Staging was based on the system of the American Joint Committee on Cancer.
Main Outcome Measures: EphB4 and EphrinB2 expression was evaluated by Western blot analysis. Overall survival in patients was then compared with EphB4 and EphrinB2 expression.
Results: EphB4 and EphrinB2 expression was detected in all normal and tumor samples in patients with HNSCC, with the magnitude of EphB4 overexpression greater than that of EphrinB2 expression compared with normal tissue. There was a statistically significant decrease in overall survival among patients with elevated EphB4 and EphrinB2 expression (P < .001).
Conclusions: EphB4 and EphrinB2 overexpression is associated with poor overall survival in patients with HNSCC. Our results are the first to demonstrate an association between decreased survival and elevated expression of the receptor tyrosine kinase EphB4 and its ligand EphrinB2, suggesting that EphB4 and EphrinB2 may be used as biomarkers to predict prognosis and as targets in future HNSCC therapies.
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http://dx.doi.org/10.1001/archotol.134.9.985 | DOI Listing |
Biochemistry
January 2025
Research and Early Development Oncology, Bayer AG, Müllerstr. 178, Berlin 13342, Germany.
The receptor tyrosine kinase EphB4 is involved in tumor angiogenesis, proliferation, and metastasis. Designed ankyrin repeat proteins (DARPins) binding to the EphB4 extracellular domain were identified from a combinatorial library using phage display. Surface plasmon resonance (SPR) allowed us to distinguish between DARPins that either compete with the EphB4 ligand ephrin-B2 for binding to a common site or target a different epitope.
View Article and Find Full Text PDFCarcinogenesis
November 2024
Priority Research Centre for Healthy Lungs, School of Biomedical Sciences and Pharmacy, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Callaghan, Australia.
Multiple primary lung tumor is garnering attention from clinicians, with adenocarcinoma emerging as the predominant histological type. Because of the heterogeneity and diffuse distribution of lesions in the same patient, the treatment of multiple primary lung adenocarcinoma (MPLA) is a significant challenge. As a kind of variation unaffected by tumor heterogeneity, germline alterations may play a key role in the development of MPLA.
View Article and Find Full Text PDFOncogene
February 2025
Department of Radiation Oncology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
The EphB4-ephrinB2 signaling axis has been heavily implicated in metastasis across numerous cancer types. Our emerging understanding of the dichotomous roles that EphB4 and ephrinB2 play in head and neck squamous cell carcinoma (HNSCC) poses a significant challenge to rational drug design. We find that EphB4 knockdown in cancer cells enhances metastasis in preclinical HNSCC models by augmenting immunosuppressive cells like T regulatory cells (Tregs) within the tumor microenvironment.
View Article and Find Full Text PDFRecently developed ultrasound contrast agents are a promising tool for imaging and drug delivery in tumors. To better understand their unusual kinetics, we implemented a novel pixel clustering analysis, which provides unique information by accounting for spatial heterogeneity. By combining ultrasound results with proteomics of the imaged tumors, we show that this analysis is highly predictive of protein expression and that specific types of nanobubble time-intensity curve are associated with upregulation of different metabolic pathways.
View Article and Find Full Text PDFUnlabelled: Head and Neck Squamous Cell Carcinoma (HNSCC) is a deadly cancer with poor response to targeted therapy, largely driven by an immunosuppressive tumor microenvironment (TME). Here we examine the immune-modulatory role of the receptor tyrosine kinase EphA4 in HNSCC progression. Within the TME, EphA4 is primarily expressed on regulatory T cells (Tregs) and macrophages.
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