EXT2: a novel prognostic and predictive biomarker for head and neck squamous cell carcinoma

Oral Surg Oral Med Oral Pathol Oral Radiol. 2024 Mar;137(3):282-289. doi: 10.1016/j.oooo.2023.11.011. Epub 2023 Nov 24.

Abstract

Objective: This study focused on EXT2, a member of the EXT family involved in heparan sulfate synthesis, to evaluate its potential as a prognostic and predictive biomarker in head-neck squamous cell carcinoma (HNSCC).

Materials and methods: The present study used the cancer genome atlas head-neck squamous cell carcinoma (TCGA-HNSC) dataset-based UALCAN database to analyze the EXT2 expression and its clinicopathological features. In addition, we recruited 51 oral squamous cell carcinoma patients (OSCC), the most common HNSCC subtype, to validate the EXT2 mRNA expression analysis. In addition, we identified the role of EXT2 in prognosis using a Kaplan-Meier plot and immune signature using the tumor infiltration level. Furthermore, functional roles were analyzed using the EXT2 gene and protein networks.

Results: The expression of EXT2 mRNA was significantly upregulated in OSCC tumors, which is consistent with the UALCAN-based results. EXT2 protein was also significantly overexpressed in HNSCC samples and was correlated with clinicopathological features. High EXT2 expression is associated with poor survival outcomes in HNSCC patients. Functional analysis of EXT2 using in silico tools revealed its involvement in critical pathways, including Wnt signaling, proteoglycans in cancer, and cellular responses to fibroblast growth and inflammation.

Conclusion: These findings highlight the potential of EXT2 as a prognostic and predictive biomarker of HNSCC.

MeSH terms

  • Biomarkers
  • Carcinoma, Squamous Cell* / genetics
  • Head and Neck Neoplasms* / genetics
  • Humans
  • Mouth Neoplasms*
  • Prognosis
  • RNA, Messenger
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Biomarkers
  • RNA, Messenger
  • exostosin-2