IJMMS_2025v15n1

International Journal of Molecular Medical Science, 2025, Vol.15, No.1, 9-19 http://medscipublisher.com/index.php/ijmms 12 biomarkers and therapeutic targets, encouraging researchers to adopt these technologies for better understanding the pathogenesis of OSCC and improving patient outcomes (Kim et al., 2020). 3.2 Liquid biopsy for circulating tumor DNA (ctDNA) and miRNAs Liquid biopsy, a minimally invasive diagnostic technique, has gained significant attention for its ability to detect circulating tumor DNA (ctDNA) and microRNAs (miRNAs) from blood, saliva, and other body fluids. This approach provides a real-time snapshot of the tumor's molecular profile without the need for traditional tissue biopsies. Lin et al. (2021) discussed the advantages of using ctDNA profiling through liquid biopsy, highlighting its utility in monitoring tumor progression and detecting early genetic alterations associated with OSCC (Lin et al., 2021). Circulating miRNAs have also emerged as promising biomarkers for early detection of oral cancer due to their stability in blood and saliva. Roi et al. (2023) reviewed the role of miRNAs as non-invasive biomarkers in oral cancer diagnosis, noting that changes in specific miRNA expression levels in plasma can serve as early indicators of malignant transformation (Roi et al., 2023). For example, miR-21 and miR-31 have been shown to be upregulated in oral cancer patients, providing potential targets for early detection. The integration of ctDNA and miRNA analysis through liquid biopsy has opened new avenues for monitoring therapeutic response and detecting Minimal Residual Disease (MRD). Cescon et al. (2020) emphasized that ctDNA analysis enables clinicians to track the evolution of tumor clones over time and adapt treatment strategies accordingly, making it a valuable tool in personalized medicine for oral cancer (Cescon et al., 2020). 3.3 Proteomics for early cancer detection Proteomics, the large-scale study of proteins, has become an important tool for identifying protein-based biomarkers for the early detection of oral cancer. Advances in mass spectrometry and protein microarray technologies have allowed researchers to profile thousands of proteins simultaneously, identifying specific patterns of protein expression that correlate with disease states. Xu et al. (2020) demonstrated the potential of salivary proteomics in detecting early-stage OSCC, identifying proteins such as IL-8 and Matrix Metalloproteinases (MMPs) that were significantly upregulated in patients compared to healthy controls (Xu et al., 2020). Proteomics approaches have also been used to discover novel therapeutic targets and develop diagnostic panels for clinical use. Blatt et al. (2023) utilized a high-throughput aptamer-based proteomic platform to identify serum proteins that serve as biomarkers for early detection of OSCC. Their findings suggest that combining multiple protein markers can improve diagnostic accuracy and serve as a foundation for developing non-invasive screening tools for clinical settings (Blatt et al., 2023). Furthermore, the integration of proteomics with other omics data, such as genomics and transcriptomics, offers a holistic view of the molecular changes associated with oral cancer. This multi-omics approach can improve the sensitivity and specificity of early detection methods and provide insights into the underlying mechanisms driving OSCC progression. This integrated approach has the potential to identify robust biomarkers that can be applied in routine clinical practice, thus enhancing early detection efforts. 4 Pathogenesis and Molecular Basis of Oral Cancer 4.1 Genomic and epigenomic changes Genomic changes, such as mutations in key oncogenes and tumor suppressor genes, are fundamental to the initiation and progression of OSCC. Frequently mutated genes in OSCC include TP53, NOTCH1, and PIK3CA, which contribute to cell cycle dysregulation, impaired apoptosis, and enhanced cell proliferation (Fang et al., 2015). Beyond single-gene mutations, copy number variations and chromosomal instability also play a role in driving tumorigenesis. For example, amplifications of chromosomal regions containing oncogenes like CCND1 (Cyclin D1) have been associated with advanced stages of OSCC (Auzair et al., 2016).

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