Exploring the Genetic Signature of Oral Tongue Squamous Cell Carcinoma using Computational Systems Biology Approaches

Bayat, Zeynab; Samie, Lida; Ansari, Moham Madmahdi; Taherkhani, Amir

doi:10.30491/jabr.2024.419473.1679

Exploring the Genetic Signature of Oral Tongue Squamous Cell Carcinoma using Computational Systems Biology Approaches

Document Type : Original Article

Authors

Zeynab Bayat ¹

Lida Samie ¹

Moham Madmahdi Ansari ¹

Amir Taherkhani ²

¹ Department of Oral and Maxillofacial Medicine, Faculty of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran.

² Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

10.30491/jabr.2024.419473.1679

Abstract

Introduction: The survival rate for oral tongue squamous cell carcinoma (OTSCC) is the lowest compared to other types of carcinomas in the oral cavity. This study aims to employ novel and robust methodologies based on bioinformatics techniques to identify differentially expressed genes in OTSCC tissues compared to normal tongue samples to shed light on the underlying causes of OTSCC.
Materials and Methods: The dataset GSE13601 was obtained from the GEO, and the OPLS-DA method was applied to identify genes differentially expressed in OTSCC tissues compared to the normal healthy oral mucosa. A protein interaction map (PIM) was constructed, and hubs were identified. Survival analysis was performed to identify prognostic hub genes. The expression levels of the identified prognostic markers were evaluated at both mRNA and protein levels. Furthermore, bioinformatics web tools were used to perform pathway and GO annotation analyses.
Results: The study revealed 154 genes differentially expressed in OTSCC, with a statistically significant p<0.001 and a |Log2 fold change |>0.585. EIF2S1, EGF, NME1, NEDD8, EIF4A1, TOP1, and PSMA4 were found to have significant prognostic roles in OTSCC. The expression levels of all the identified prognostic markers were confirmed in HNSCC at the mRNA level and further validated the up-regulation of NME1, TOP1, and PSMA4 in HNSCC using immunohistochemical analysis. The FOXM1 was identified as the most important regulator of the hubs, while CDK2 was found to be the protein kinase acting on the transcription factors. The proteasome pathway and the regulation of ubiquitin-protein ligase activity were significantly enriched in OTSCC.
Conclusions: This study provides valuable insights into the pathogenesis of OTSCC and may assist in improving the prognosis of OTSCC patients.

Keywords

Biomarkers

Cancer

Oral

Prognosis

Tongue