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.
Oncol Rep. 2022 Oct;48(4). doi: 10.3892/or.2022.8398. Epub 2022 Sep 9.
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.
本研究旨在探讨 Src 相关在有丝分裂 68 kDa（Sam68）在口腔鳞状细胞癌（OSCC）中的临床和生物学意义。对 77 例 OSCC 患者的组织样本进行免疫组织化学分析。单因素分析显示，Sam68 高表达与晚期病理 T 分期（P=0.01）、阳性脉管浸润（P=0.01）和病理颈淋巴结转移（P<0.01）显著相关。此外，多因素分析表明，Sam68 高表达是颈淋巴结转移的独立预测因子（比值比，4.39；95%置信区间，1.49-14.23；P<0.01）。这些结果表明，Sam68 高表达促进了 OSCC 的肿瘤进展，特别是颈淋巴结转移。还进行了 mRNA 测序，以评估 Sam68 敲低的 OSCC 细胞与对照细胞之间转录组的变化，旨在阐明 Sam68 的生物学作用。基因本体富集分析显示，下调的差异表达基因（DEGs）集中在一些与上皮-间充质转化相关的生物学过程中。在这些 DEGs 中，发现波形蛋白在这些细胞中表达特别下调。还证实 Sam68 敲低降低了 OSCC 细胞的迁移能力。此外，波形蛋白的免疫组织化学研究确定了波形蛋白表达与 Sam68 表达以及颈淋巴结转移之间的关联。总之，本研究表明，Sam68 的高表达可能通过调节 OSCC 中的波形蛋白表达和运动性间充质表型来促进转移。
