Moriya Yujiro, Uzawa Narikazu, Morita Takuma, Mogushi Kaoru, Miyaguchi Ken, Takahashi Ken-Ichiro, Michikawa Chieko, Sumino Jun, Tanaka Hiroshi, Harada Kiyoshi
Maxillofacial Surgery, Maxillofacial Reconstruction and Function, Division of Maxillofacial and Neck Reconstruction, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Computational Biology, Graduate School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
Oral Oncol. 2015 Jan;51(1):84-9. doi: 10.1016/j.oraloncology.2014.10.001. Epub 2014 Oct 24.
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).
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.
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).
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.
以往研究已鉴定出多个参与口腔癌致癌过程的基因；然而，这一过程背后的详细机制尚未阐明。此前，我们建立了一个口腔癌发生转录进展图谱数据库，并鉴定出15个表达持续增加或减少的候选基因（Sumino等人，2013年）。
在本研究中，利用该数据库，我们试图鉴定可能对从口腔发育异常病变进展为浸润性肿瘤有特异性作用的基因。
我们鉴定出4个候选基因。通过文献调研，我们缩小了候选范围，并聚焦于高温需求因子A3（HtrA3）。定量实时逆转录聚合酶链反应和免疫组化分析证实，在此过程中HtrA3表达显著增加。此外，HtrA3高表达与无病生存期降低（P = 0.045）和总生存期降低（P = 0.003）显著相关。多变量Cox比例风险分析发现，HtrA3高表达与总生存期显著相关（P = 0.018）。
本研究结果表明，HtrA3可能与口腔鳞状细胞癌细胞侵袭表型的获得有关，可能是口腔癌的一个潜在预后标志物。
