The high-temperature requirement factor A3 (HtrA3) is associated with acquisition of the invasive phenotype in oral squamous cell carcinoma cells

Abstract

Objectives: Previous studies have identified several genes involved in the carcinogenesis of oral cancer; however, the detailed mechanisms underlying this process have not been elucidated. Previously, we established a database of the transcriptional progression profile of oral carcinogenesis and identified 15 candidate genes with continuously increasing or decreasing expression (Sumino et al., 2013).

Materials and methods: In the present study, using this database, we attempted to identify genes that may specifically contribute to progression from oral dysplastic lesions to invasive tumours.

Results: We identified 4 candidate genes. Using a literature survey, we narrowed down the candidates and focused on the high-temperature requirement factor A3 (HtrA3). Quantitative real-time reverse transcription polymerase chain reaction and immunohistochemical analysis confirmed that HtrA3 expression significantly increased during this process. In addition, high HtrA3 expression was significantly associated with decreased disease-free survival (P=0.045) and overall survival (P=0.003). Multivariate Cox proportional hazards analysis found that high HtrA3 expression significantly correlated with overall survival (P=0.018).

Conclusion: The findings of this study demonstrated that the HtrA3 is likely to be associated with the acquisition of the invasive phenotype in oral squamous cell carcinoma cells and may be a potential prognostic marker for oral cancer.

Keywords: Carcinogenesis; HtrA3; Laser microdissection; Microarray; Oral; Squamous cell carcinoma.