Department of Oral Oncology, Oral and Maxillofacial Surgery, Tokyo Dental College, Chiyoda, Japan.
Oral Cancer Center, Tokyo Dental College, Chiyoda, Japan.
Int J Clin Oncol. 2023 Sep;28(9):1129-1138. doi: 10.1007/s10147-023-02374-2. Epub 2023 Jul 7.
Secondary lymph node metastasis (SLNM) indicates a poor prognosis, and limiting it can improve the survival rate in early-stage tongue squamous cell carcinoma (TSCC). Many factors have been identified as predictors of SLNM; however, there is no unified view. Ras-related C3 botulinum toxin substrate 1 (Rac1) was found to be a promoter of the epithelial-mesenchymal transition (EMT) and is also attracting attention as a new therapeutic target. This study aims to investigate the role of Rac1 in metastasis and its relationship with pathological findings in early-stage TSCC.
Rac1 expression levels of 69 cases of stage I/II TSCC specimens and their association with clinicopathological characteristics were evaluated by immunohistochemical staining. The role of Rac1 in oral squamous cell carcinoma (OSCC) was examined after Rac1 in OSCC cell lines was silenced in vitro.
High Rac1 expression was significantly associated with the depth of invasion (DOI), tumor budding (TB), vascular invasion, and SLNM (p < 0.05). Univariate analyses revealed that Rac1 expression, DOI, and TB were factors significantly associated with SLNM (p < 0.05). Moreover, our multivariate analysis suggested that Rac1 expression was the only independent determinant of SLNM. An in vitro study revealed that Rac1 downregulation tended to decrease cell migration and proliferation.
Rac1 was suggested to be an important factor in the metastasis of OSCC, and it could be useful as a predictor of SLNM.
二级淋巴结转移（SLNM）预示着预后不良，限制其发生可以提高早期舌鳞癌（TSCC）的生存率。许多因素已被确定为 SLNM 的预测因子，但尚无统一的观点。Ras 相关 C3 肉毒杆菌毒素底物 1（Rac1）被发现是上皮-间充质转化（EMT）的促进剂，作为一种新的治疗靶点也引起了关注。本研究旨在探讨 Rac1 在转移中的作用及其与早期 TSCC 病理发现的关系。
通过免疫组织化学染色评估 69 例 I/II 期 TSCC 标本中 Rac1 的表达水平及其与临床病理特征的关系。体外沉默 OSCC 细胞系中的 Rac1 后，研究 Rac1 在口腔鳞状细胞癌（OSCC）中的作用。
高 Rac1 表达与浸润深度（DOI）、肿瘤芽（TB）、血管侵犯和 SLNM 显著相关（p<0.05）。单因素分析显示，Rac1 表达、DOI 和 TB 是与 SLNM 显著相关的因素（p<0.05）。此外，多因素分析提示 Rac1 表达是 SLNM 的唯一独立决定因素。体外研究表明 Rac1 下调可降低细胞迁移和增殖。
Rac1 被认为是 OSCC 转移的重要因素，可能作为 SLNM 的预测因子有用。
