Assessment of DUSP1 Expression Levels in Tumor and Surgical Margin Samples of Laryngeal Squamous Cell Carcinoma

Document Type : Original Article

Authors

1 Assistant Professor of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

2 Associate Professor of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Abstract
Introduction: Laryngeal squamous cell carcinoma remains a major clinical challenge, and conventional margin assessment may overlook molecular alterations associated with residual disease and field cancerization. DUSP1, a regulator of MAPK signaling, may contribute to tumor behavior. This study aimed to assess DUSP1 expression levels in tumor and surgical margin samples of LSCC.

Material and methods: This descriptive cross-sectional study was conducted in 2024 at Tabriz University of Medical Sciences on 50 patients with laryngeal squamous cell carcinoma, selected through convenience sampling based on the Cochran formula for single-group studies. DUSP1 expression was measured in paired tumor and surgical margin samples, alongside demographic, clinical, and pathological variables, including age, sex, smoking status, tumor site, grade, TNM stage, lymph node involvement, and margin status.

Results: In this study of 50 patients with laryngeal squamous cell carcinoma, mean DUSP1 expression was significantly higher in tumor tissue than in paired surgical margins (2.73 ± 0.68 vs. 1.41 ± 0.37; P=0.001). Tumoral DUSP1 expression was also greater in smokers, poorly differentiated tumors, advanced-stage disease, node-positive cases, and positive surgical margins, indicating a consistent association between elevated DUSP1 levels and more aggressive clinicopathological characteristics.

Conclusion: DUSP1 was significantly overexpressed in LSCC tumor tissue compared with surgical margins and was associated with adverse clinicopathological features. These findings suggest that DUSP1 may serve as a promising molecular indicator of tumor aggressiveness and local disease extension.

Graphical Abstract

Assessment of DUSP1 Expression Levels in Tumor and Surgical Margin Samples of Laryngeal Squamous Cell Carcinoma

Keywords

Subjects

[1]       Steuer, C. E., et al. (2023). The evolving landscape of salivary gland tumors. CA: A Cancer Journal for Clinicians, *73*, 597-619.
[2]       Renehan, A., Gleave, E. N., Hancock, B. D., Smith, P., & McGurk, M. (1996). Long-term follow-up of over 1000 patients with salivary gland tumours treated in a single centre. British Journal of Surgery, *83*, 1750-1754.
[4]       Williams, M. D., & Tischler, A. S. (2017). Update from the 4th edition of the World Health Organization classification of head and neck tumours: Paragangliomas. Head and Neck Pathology, *11*, 88-95.
[7]       Mezi, S., et al. (2020). Primary squamous cell carcinoma of major salivary gland: "Sapienza head and neck unit" clinical recommendations. Rare Tumors, *12*, 2036361320973526.
[8]       Meyer, M. F., et al. (2021). Survival after parotid gland metastases of cutaneous squamous cell carcinoma of the head and neck. Oral and Maxillofacial Surgery, *25*, 383-388.
[9]       Praktiknjo, S. D., et al. (2020). Tracing tumorigenesis in a solid tumor model at single-cell resolution. Nature Communications, *11*, 991.
[10]    Wend, P., et al. (2013). Wnt/β-catenin signaling induces MLL to create epigenetic changes in salivary gland tumours. The EMBO Journal, *32*, 1977-1989.
[11]    Hedberg, M. L., et al. (2022). Molecular mechanisms of cutaneous squamous cell carcinoma. International Journal of Molecular Sciences, *23*, 3478.
[12]    Hammouda, M. B., Ford, A. E., Liu, Y., & Zhang, J. Y. (2020). The JNK signaling pathway in inflammatory skin disorders and cancer. Cells, *9*, 857.
[13]    Shen, J., et al. (2016). Role of DUSP1/MKP1 in tumorigenesis, tumor progression and therapy. Cancer Medicine, *5*, 2061-2068.
[14]    Siegle, J. M., et al. (2014). SOX2 is a cancer-specific regulator of tumour initiating potential in cutaneous squamous cell carcinoma. Nature Communications, *5*, 4511.
[15]    Molina, G., et al. (2009). Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages. Nature Chemical Biology, *5*, 680-687.
[17]    Tanaka, T., et al. (2016). Bmi1-positive cells in the lingual epithelium could serve as cancer stem cells in tongue cancer. Scientific Reports, *6*, 39386.
[18]    Qi, X., et al. (2019). KLF4 functions as an oncogene in promoting cancer stem cell-like characteristics in osteosarcoma cells. Acta Pharmacologica Sinica, *40*, 546-555.
[19]    Chattopadhyay, S., et al. (2006). MKP1/CL100 controls tumor growth and sensitivity to cisplatin in non-small-cell lung cancer. Oncogene, *25*, 3335-3345.
[20]    Moncho-Amor, V., et al. (2011). DUSP1/MKP1 promotes angiogenesis, invasion and metastasis in non-small-cell lung cancer. Oncogene, *30*, 668-678.
[21]    Bou Mahdi, S., et al. (2014). SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma. Nature, *511*, 246-250.
[22]    Pastushok, I., & Blanpain, C. (2018). EMT transition states during tumor progression and metastasis. Trends in Cell Biology, *29*, 212-226.
[24]    Tanaka, T., et al. (2013). Identification of stem cells that maintain and regenerate lingual keratinized epithelial cells. Nature Cell Biology, *15*, 511-518.
[27]    Farahzadi, R., et al. (2023). Oxidative stress regulation and related metabolic pathways in epithelial mesenchymal transition of breast cancer stem cells. Stem Cell Research & Therapy, *14*, 342.
[28]    Driehaus, E., Kretzschmar, K., & Clevers, H. (2020). Establishment of patient-derived cancer organoids for drug-screening applications. Nature Protocols, *15*, 3380-3409.
[29]    Anders, S., Pyl, P. T., & Huber, W. (2015). HTSeq—A Python framework to work with high-throughput sequencing data. Bioinformatics, *31*, 166-169.
[30]    Sadeghi Joni, S., Gerami, R., Akhondi, N., Etemadi, A., Fosouli, M., & Eghbal, A. F. (2022). Investigating the role of susceptibility weighted imaging for assessment of ischemic penumbra with respect to Venus's blood flow in ischemic stroke patients. International Journal of Physiology, Pathophysiology and Pharmacology, *14*(3), 200-205.