Transcriptome Analysis and Histological Validation Identified the <scp>HO</scp> ‐1‐ <scp>u</scp> ‐1 Cell Line as a Model for Perineural Invasion in Oral Squamous Cell Carcinoma

BACKGROUND: Perineural invasion (PNI) is a pathological feature of oral squamous cell carcinoma (OSCC) that is associated with a poor prognosis. However, the molecular mechanisms remain poorly understood. The aim of this study was to establish an in vivo model to explore PNI in OSCC. METHODS: We performed an integrated analysis of The Cancer Genome Atlas transcriptome data from tongue squamous cell carcinoma (TSCC) and floor of the mouth squamous cell carcinoma (FOMSCC) by the presence of PNI and identified differentially expressed genes (DEGs). We also performed xenografts of five OSCC cell lines (OSC19, OSC20, HSC2, KOSC2, and HO-1-u-1) into nude mouse tongues and assessed PNI histology. Furthermore, transcriptome profiles of the cell lines were analyzed to identify cell line-specific genes associated with PNI. RESULTS: Among OSCCs, PNI cases were more prevalent in TSCC and FOMSCC. Expression analysis detected 103 DEGs in TSCC and 401 in FOMSCC. In TSCC, 42.2% of the DEGs were non-coding RNAs, whereas DEGs in FOMSCC were predominantly protein-coding genes enriched in pathways related to muscle contraction and fibrosis. Xenograft analysis revealed that HO-1-u-1 uniquely exhibited a nerve-directed invasion phenotype. Transcriptome analysis of OSCC cell lines demonstrated that HO-1-u-1 was enriched in neural- and glial-related pathways, consistent with its neurotropic behavior in vivo. CONCLUSIONS: Our transcriptome analysis suggested that different pathways might drive PNI in TSCC and FOMSCC, depending on their origin. We also demonstrated that HO-1-u-1 is a unique OSCC cell line with strong neurotropic properties and a valuable xenograft model for OSCC PNI.