Diagnostic, prognostic, and metastatic value of chemokines as biomarkers for oral squamous cell carcinoma and their precursor lesions – A systematic review

Abstract

Oral cancer remains a significant public health concern, with many patients diagnosed at advanced stages and facing poor prognoses. Despite advances in cancer research, diagnosis has seen only limited improvements, with biopsies still being the primary reliable method. This systematic review investigates the role of chemokines as potential biomarkers for early detection, prognosis, and metastasis in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). Through an extensive literature search of MEDLINE, EMBASE, PubMed, and Scopus, 3350 articles were initially identified. After eliminating duplicates and screening for eligibility, 50 high-quality studies were included, offering a comprehensive overview of chemokine research in OSCC and OPMDs. Key findings indicate that CCR7 shows significant promise as a diagnostic, prognostic, and metastatic marker, although its function in precancerous conditions remains inadequately understood. CXCL10 and CCL22 were also highlighted for their strong prognostic and metastatic relevance, while CXCR4 and CXCL12 were identified as critical indicators of OSCC metastasis. Other chemokines, such as CXCR2, CCR4, XCR1, CXCL13, and CCL2 can aid OSCC differentiation and staging. However, the review emphasises the limitations of small patient cohorts and the lack of longitudinal research, stressing the need for further studies. Additionally, there is a pressing gap in research addressing chemokines as biomarkers for OPMDs. Rigorous validation is crucial to establish these biomarkers’ reliability and clinical utility across various stages of oral cancer development.