Mitochondrial metabolism-associated biomarkers in oral lichen planus and oral squamous cell carcinoma

Oral lichen planus (OLP), a chronic inflammatory condition, is classified as a potentially malignant disorder due to its risk of progression to oral squamous cell carcinoma (OSCC). Mitochondrial metabolism plays a key role in pathogenesis and progression of OSCC. This study aimed to identify and validate biomarkers associated with mitochondrial metabolism-related genes (MRGs) in OLP and OSCC, thereby contributing to the development of novel therapeutic strategies. Transcriptomic data from OLP (GSE38616, GSE52130) and OSCC (GSE30784, GSE25099) datasets were analyzed. Differentially expressed genes were intersected with known MRGs to identify candidate biomarkers. These genes were further validated through expression analyses within the respective datasets. A predictive nomogram was constructed based on selected biomarkers and assessed for diagnostic performance. Functional enrichment analysis, immune cell infiltration profiling, pharmacological targeting prediction, molecular docking, and reverse transcription quantitative PCR (RT-qPCR) validation were performed to elucidate underlying biological mechanisms. Three biomarkers ALDH3A2, CYP11A1, and IMPDH2 were identified as significantly associated with both OLP and OSCC. Expression levels of these genes were significantly reduced in affected tissues compared to unaffected control tissues, a finding confirmed through RT-qPCR analysis. A nomogram incorporating these biomarkers effectively predicted OSCC risk. Functional enrichment analysis indicated co-enrichment of these genes in the olfactory transduction pathway in OLP and the ECM-receptor interaction pathway in OSCC. Analysis of immune infiltration identified 22 differentially abundant immune cell types in OSCC versus control samples, with ALDH3A2 exhibiting a strong inverse correlation with natural killer T cell levels. A total of 29 candidate compounds targeting these biomarkers were identified; among them, IMPDH2 presented a binding energy of - 10.6 kcal/mol with AC1NRCGS, indicating potential therapeutic relevance. ALDH3A2, CYP11A1, and IMPDH2 were validated as potential biomarkers linked to mitochondrial metabolism in patients with OLP and OSCC. These findings provide a foundation for further exploration of targeted treatment strategies in the management of OLP and OSCC.