Abstract
Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93–7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann–Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in developed countries [1, 2]
Loss of RAB25 expression is associated with poor survival in patients with locally advanced head and neck carcinoma
Our findings show that RAB25 expression is associated with clinical outcome in patients with locally advanced head and neck carcinoma
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in developed countries [1, 2]. Chemotherapy combined with radiotherapy (RT) and/or surgery has increased organ preservation and improved locoregional control in locally advanced patients [3]. Response to induction chemotherapy (IC) and the infection by human papillomavirus (HPV) are the only markers used in locally advanced HNSCC treatment decisions [7,8,9]. Regarding HPV, its prognostic and predictive value is limited to oropharyngeal HNSCC and because of the wide variation in the incidence of HPV infection, depending on the geographic region [10]. The development of new molecular markers associated with clinical outcome in HNSCC could be useful in selecting the most appropriate treatment for each patient and to improve their follow-up
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