Screening Differentially Expressed Proteins in Areca Nut-Related Oral Squamous Cell Carcinoma Using Tandem Mass Tag Proteomics

Int Dent J. 2025 Jan 4:S0020-6539(24)01635-6. doi: 10.1016/j.identj.2024.12.017. Online ahead of print.

Abstract

Objective: Areca nut chewing has been associated with a poor prognosis in oral squamous cell carcinoma (OSCC). This study seeks to identify differentially expressed proteins among areca nut-related OSCC,non-areca nut-related OSCC and adjacent normal epithelial tissues, with the aim of providing novel insights for the investigation of areca nut-related OSCC.

Methods: Using Tandem mass tag (TMT)-based proteomic analysis, a comparative proteomic profiling was conducted among areca nut-related OSCC, non-areca nut-related OSCC, and adjacent normal epithelial tissues (n=15). GO and KEGG enrichment analyses were then employed to identify significant proteins pertinent to the pathogenesis of OSCC for further study. Western Blot (WB) and Immunohistochemistry (IHC) techniques were used to preliminary validate the expression patterns of LZTS1, MMP10, MYH6, MB, and TNNC1 among various groups (n=30).

Results: 27 differentially expressed proteins were identified when comparing the areca nut-related OSCC group with both the non-areca nut-related OSCC and normal epithelial tissue groups. Among these, 15 proteins were upregulated, while 12 were downregulated. LZTS1 and MMP10 were included in the upregulated proteins, whereas MYH6, MB, and TNNC1 were downregulated. WB and IHC analyses corroborated the proteomic findings, revealing consistent expression trends for these 5 proteins across the studied groups.

Conclusion: LZTS1, MMP10, MYH6, MB and TNNC1 emerge as promising biomarkers for assessing disease progression, prognosis, and potential targeted therapies in areca nut-related OSCC.

Keywords: Areca nut; Biomarkers; Oral squamous cell carcinoma (OSCC); Proteomics; Tandem mass tag (TMT).