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Rac1 activation in oral squamous cell carcinoma as a predictive factor associated with lymph node metastasis

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Abstract

Objectives

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.

Materials and methods

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.

Results

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.

Conclusion

Rac1 was suggested to be an important factor in the metastasis of OSCC, and it could be useful as a predictor of SLNM.

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Abbreviations

DFS:

Disease-free survival

DOI:

Depth of invasion

EMT:

Epithelial-mesenchymal transition

END:

Elective neck dissedtion

HR:

Hazard retios

NCCN:

National Comprehensive Cancer Network

OSCC:

Oral squamous cell carcinoma

PBS:

Phosphate-buffered saline

ROC:

Receiver operating characteristics

TSCC:

Tongue squamous cell carcinoma

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Acknowledgements

The authors thank Kazunari Higa and Junichirou Inada for their support and technical assistance

Author information

Authors and Affiliations

  1. Department of Oral Oncology, Oral and Maxillofacial Surgery, Tokyo Dental College, Chiyoda, Japan

    Masae Yamazaki, Taiki Suzuki & Takeshi Nomura

  2. Oral Cancer Center, Tokyo Dental College, Chiyoda, Japan

    Shoichi Sekikawa, Taiki Suzuki & Takeshi Nomura

  3. Department of Plastic, Oral and Maxillofacial Surgery, Teikyo University School of Medicine, Itabashi, Japan

    Satoru Ogane

  4. Department of Pathology and Laboratory Medicine, Ichikawa General Hospital, Tokyo Dental College, Chiyoda, Japan

    Kazuhiko Hashimoto & Aya Sasaki

Authors
  1. Masae Yamazaki
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  2. Shoichi Sekikawa
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  3. Taiki Suzuki
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  4. Satoru Ogane
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  5. Kazuhiko Hashimoto
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  7. Takeshi Nomura
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Contributions

MY, TN: Study concepts, Study design, MY,TS: Data acquisition, MY, KH, HS: Quality control of data and algorithms, MY, SS: Data analysis and interpretation, MY, SO: Statistical analysis, MY, SS, SO: Manuscript preparation, MY, TS: Manuscript editing, MY, TN: Manuscript review.

Corresponding author

Correspondence to Masae Yamazaki.

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Yamazaki, M., Sekikawa, S., Suzuki, T. et al. Rac1 activation in oral squamous cell carcinoma as a predictive factor associated with lymph node metastasis. Int J Clin Oncol 28, 1129–1138 (2023). https://doi.org/10.1007/s10147-023-02374-2

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  • DOI: https://doi.org/10.1007/s10147-023-02374-2

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