[P1-2-42] Expression profiles of Semaphorin signaling-related genes that control perineural invasion of oral cancer.
Keywords:口腔扁平上皮癌、神経周囲浸潤、セマフォリン3
Objectives Squamous cell carcinoma of head and neck, is known to have a high incidence of Perineural Invasion (PNI), a phenomenon that increases the likelihood of metastasis, recurrence and ultimately has a negative impact on prognosis. Recently, Semaphorin 3 subfamily (SEMA3s), well-known axon guidance factors, has been reported to be involved in PNI, but its role in oral squamous cell carcinoma (OSCC) is still unknown. To elucidate the underlying mechanism of PNI, we performed in silico as well as in vitro analyses for SEMA3s and related genes as possible regulators of PNI in OSCC. Materials & Methods RNA-seq data on oral cancer specimens were obtained from the TCGA database (Cancer Genome Atlas) and comparison analysis of PNI (-) and PNI (+) OSCC patients were performed. Quantitative gene expression analyses for SEMA3s and their receptors PLXN family and NRP family were performed by q-PCR using RNAs from human OSCC-derived cell lines OSC19, OSC20, HSC2, KOSC2, HO-1-u-1, and immortalized gingival keratinocytes as a control. Results & Discussion Comparative analysis of RNA-seq data revealed activation of Semaphorin signaling in PNI (+) oral cancer patients, in particular, SEMA3D was significantly upregulated. q-PCR analyses revealed significant differences in the expression levels of NRP and PLXN subfamilies in addition to SEMA3s and elucidated the existence of diverse expression patterns of Semaphorin signaling for each cell line. These findings suggested that oral cancer cells may construct an own autocrine signaling pathway of SEMA3s, and that cell line-specific Semaphorin signaling pathway may be involved in PNI activity in oral cancer.