Abstract A036: DDR2 expression is associated with poor prognosis in head and neck squamous cell carcinoma

• Published in: Molecular cancer therapeutics 2018-01, Vol.17 (1_Supplement), p.A036-A036
• Main Authors: Matos e Silva, Flavia Amoroso, Klug, Katia, Coutinho-Camillo, Claudia Malheiros, Kowalski, Luiz Paulo, Soares, Fernando Augusto
• Format: Article
• Language: English
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.TARG-17-A036

Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor of epithelial keratinocytes that represents a growing public health problem. It is one of the most common solid cancers worldwide with rate of 9.2/100,000 people. In 2016, the estimate in Brazil is 6.3/100,000 men and 3.4/100,000 women. The prognosis is poor, especially once it recurs or metastasizes. Current therapeutic options include surgery, radio- and/or chemotherapy. Targeted therapy holds great promise of improving patient outcome while limiting toxicity and treatment exposure. Understanding the molecular cancer pathways of underlying HNSCC metastasis would help to improve the therapy of the disease. Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase (RTK) that can be activated by fibrillar collagens and implicated in several cancer cell behaviors, including VEGF expression, tumor angiogenesis, invasion, and metastasis. Matrix metalloproteinases (MMPs) are an important subset of downstream target genes of DDR2 signaling. Though previous studies have investigated the function of DDR2 in some common tumors, there has not been functional characterization of the potential role of DDR2 in HNSCC. Therefore, the aim of the current study was to investigate this issue. The general objective of this project is to verify the potential DDR2 gene as tumor markers and therapeutic target in HNSCC. In this study, DDR2 expression was examined by immunohistochemistry in 50 HNSCC patients, and the correlation between DDR2 expression with clinicopathologic factors was analyzed. The result showed DDR2 expression in all the nucleus, cytoplasm, and membrane in HNSCC patients. Statistical analysis revealed that DDR2 expression is associated with overall survival and recurrent-free survival. Patients with high DDR2 expression in the nucleus showed 6-fold higher risk of death compared to patients with a low level of DDR2 expression (p = 0,003) and 40-fold more chance of recurrence (p = 0,001). High DDR2 expression in the cytoplasm showed a 2.2-fold higher risk of death compared to patients with a low level (p = 0,026) and 47-fold more chance of recurrence (p = 0,006). In relation to plasma membrane, high DDR2 expression the results showed a 3.8-fold higher risk of death compared to patients with a low level (p = 0,008) and 6.5-fold more chance of recurrence (p = 0,009). In conclusion, these data suggest that DDR2 expression may be a prognostic indicator and a useful therapeutic target. Citation