Salivary Lactate Dehydrogenase, Matrix Metalloproteinase-9, and Chemerin—The Most Promising Biomarkers for Oral Cancer? A Systematic Review with Meta-Analysis

Oral cancer (OC) constitutes a significant health problem globally. There is an urgent need to develop novel biomarkers for OC diagnosis. This meta-analysis aimed to analyze the potential of salivary lactate dehydrogenase (LDH), matrix metalloproteinase-9 (MMP-9), and chemerin as OC biomarkers. The meta-analysis was conducted according to the PRISMA statement guidelines and registered in PROSPERO (CRD420251045968). PubMed, Embase, Scopus, and Web of Science databases were thoroughly searched up to 18 April 2025. After screening, thirty-three articles were included in the meta-analysis based on the random-effects model. The meta-analysis revealed a significantly elevated LDH level in OC patients compared with controls (SMD = 4.592, 95% CI: 3.580–5.605, p < 0.001) and with oral potentially malignant disorders (OPMD) (SMD = 2.416, 95% CI: 1.474–3.358, p < 0.001). For poorly versus well-differentiated OC, significantly higher LDH levels were observed in poorly differentiated tumors (SMD = 6.158, 95% CI: 0.739–11.576, p = 0.027). For MMP-9, there was a significant increase in OC compared with controls and a borderline-significant difference compared with OPMD (SMD = 1.507, 95% CI: 0.644–2.369, p = 0.001; SMD = 1.626, 95% CI: −0.097–3.350, p = 0.064, respectively). In comparing poorly versus well-differentiated OC, MMP-9 levels were significantly increased in poorly differentiated tumors (SMD = 1.790, 95% CI: 0.643–2.937, p = 0.003). Chemerin levels were significantly elevated in OC versus controls (SMD = 3.905, 95% CI: 3.210–4.600, p < 0.001) and OPMD (SMD = 1.605, 95% CI: 1.139–2.071, p < 0.001). In conclusion, these findings support the potential use of LDH, MMP-9, and chemerin as adjunctive biomarkers in diagnosing and stratifying OC.