High expression of Sam68 contributes to metastasis by regulating vimentin expression and a motile phenotype in oral squamous cell carcinoma

Komiyama,Takuya; Kuroshima,Takeshi; Sugasawa,Takehito; Fujita,Shin-Ichiro; Ikami,Yuta; Hirai,Hideaki; Tsushima,Fumihiko; Michi,Yasuyuki; Kayamori,Kou; Higashino,Fumihiro; Harada,Hiroyuki

doi:10.3892/or.2022.8398

High expression of Sam68 contributes to metastasis by regulating vimentin expression and a motile phenotype in oral squamous cell carcinoma

Authors:
- Takuya Komiyama
- Takeshi Kuroshima
- Takehito Sugasawa
- Shin-Ichiro Fujita
- Yuta Ikami
- Hideaki Hirai
- Fumihiko Tsushima
- Yasuyuki Michi
- Kou Kayamori
- Fumihiro Higashino
- Hiroyuki Harada
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Affiliations: Department of Oral and Maxillofacial Surgical Oncology, Division of Health Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo‑ku, Tokyo 113‑8549, Japan, Laboratory of Clinical Examination/Sports Medicine, Department of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305‑8577, Japan, Department of Oral Pathology, Division of Oral Health Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo‑ku, Tokyo 113‑8549, Japan, Department of Molecular Oncology, Faculty of Dental Medicine and Graduate School of Biomedical Science and Engineering, Hokkaido University, Sapporo, Hokkaido 060‑8586, Japan
Published online on: September 7, 2022 https://doi.org/10.3892/or.2022.8398
Article Number: 183
Copyright: © Komiyama et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the clinical and biological significance of Src‑associated in mitosis 68 kDa (Sam68) in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis was performed on tissue samples obtained from 77 patients with OSCC. Univariate analysis revealed that the high expression of Sam68 was significantly correlated with advanced pathological T stage (P=0.01), positive lymphovascular invasion (P=0.01), and pathological cervical lymph node metastasis (P<0.01). Moreover, multivariate analysis demonstrated that the high expression of Sam68 was an independent predictive factor for cervical lymph node metastasis (odds ratio, 4.39; 95% confidence interval, 1.49‑14.23; P<0.01). These results indicated that high Sam68 expression contributed to tumor progression, especially cervical lymph node metastasis, in OSCC. mRNA sequencing was also performed to assess the changes in the transcriptome between OSCC cells with Sam68 knockdown and control cells with the aim of elucidating the biological roles of Sam68. Gene Ontology enrichment analysis revealed that downregulated differentially expressed genes (DEGs) were concentrated in some biological processes related to epithelial‑mesenchymal transition. Among these DEGs, it was established that vimentin was particularly downregulated in these cells. It was also confirmed that Sam68 knockdown reduced the motility of OSCC cells. Furthermore, the immunohistochemical study of vimentin identified the association between vimentin expression and Sam68 expression as well as cervical lymph node metastasis. In conclusion, the present study suggested that the high expression of Sam68 may contribute to metastasis by regulating vimentin expression and a motile mesenchymal phenotype in OSCC.

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