Oral squamous cell carcinoma (OSCC) is one of the most common malignancies of the head and neck squamous cell carcinoma (HNSCC). HNSCC is recognized as the eighth most commonly occurring cancer globally in men. It is essential to distinguish between cancers arising in the head and neck regions due to significant differences in their etiologies, treatment approaches, and prognoses. As the Cancer Genome Atlas (TCGA) dataset is available in HNSCC, the survival analysis prognosis of OSCC patients based on the TCGA dataset for discovering gene expression-based prognostic biomarkers is limited. To address this paucity, we aimed to provide comprehensive evidence by recruiting studies that have reported new biomarkers/signatures to establish a prognostic model to predict the survival of OSCC patients. Using PubMed search, we have identified 34 studies that have been using the least absolute shrinkage and selection operator (LASSO)-based Cox regression analyses to establish signature prognosis that related to different pathways in OSCC from the past 4 years. Our review was focused on summarizing these signatures and implications for targeted therapy using FDA-approved drugs. Furthermore, we conducted an analysis of the LASSO Cox regression gene signatures. Our findings revealed 13 studies that correlated a greater number of regulatory T cells (Tregs) cells in protective gene signatures with increased recurrence-free and overall survival rates. Conversely, two studies displayed an opposing trend in cases of OSCC. We will also explore how the dysregulation of these signatures impacts immune status, promoting tumor immune evasion or, conversely, enhancing immune surveillance. Overall, this review will provide new insight for future anti-cancer therapies based on the potential gene that is associated with poor prognosis in OSCC.

Oral potentially malignant disorders (OPMD) are a group of lesions carrying the risk of developing into cancer. The gold standard to predict which lesions are more likely to undergo malignant transformation is the presence of dysplasia histologically. However, not all dysplastic lesions progress, and non-dysplastic lesions may also undergo malignant transformation. Oral carcinogenesis is a complex molecular process that involves somatic alterations and the deregulation of transcriptions, protein expression, and metabolite levels. Metabolomics, which is the scientific study of metabolites, has emerged as a promising high-throughput approach to investigate the metabolic changes of small molecules in biological pathways. In this review, we summarize the data relating to the metabolomic profiling of OPMDs, which will help elucidate the complex process of oral carcinogenesis. Furthermore, we identify that among all metabolites, citrate, pyruvate, and glutamate may serve as potential biomarkers for oral leukoplakia (OLK). Notably, metformin and gluconate have been shown to target glutamate and citrate, respectively, in cancer cells. Based on these findings, we propose that targeting these metabolites in patients with OPMD could be a promising therapeutic strategy to mitigate OPMD progression and potentially reduce the risk of malignant transformation. We also discuss the limitations and future directions of metabolomics in OPMD. Understanding these important metabolites is crucial for early detection and monitoring of oral cancer progression.