CD44 overexpression as a mediator of drug resistance in oral cancer: a meta-analysis unveiling molecular underpinnings and therapeutic implications.

BACKGROUND

Therapeutic resistance in oral cancer, with cancer stem cells (CSCs) playing a pivotal role, remains a major clinical challenge. CD44, a key CSC marker, has been implicated in multidrug resistance mechanisms through drug efflux, DNA repair, and anti-apoptotic pathways. This meta-analysis aims to systematically evaluate the association between CD44 expression and clinicopathological characteristics in oral cancer patients through analysis of controlled clinical studies.

METHODS

We systematically searched PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, VIP, WanFang, and China Biomedical Literature Database from inception to September 2022. Controlled clinical studies examining CD44 overexpression in relation to clinicopathological characteristics and survival outcomes in oral cancer patients were included. Quality assessment was performed using the Newcastle-Ottawa Scale. Data were analyzed using RevMan 5.3 software.

RESULTS

Ten high-quality studies comprising 846 oral cancer patients were included. CD44 overexpression was significantly associated with advanced local tumor invasion (T category: OR: 1.38; 95% CI 1.14-1.66; P < 0.001; I²=25%). No significant associations were found with N category, histological grade, or vascular invasion. Pooled survival analysis was limited by heterogeneous reporting methods across studies.

CONCLUSION

CD44 overexpression serves as a molecular marker of therapeutic resistance in oral cancer, particularly associated with local tumor progression. These findings highlight CD44-targeted therapies as promising strategies to overcome treatment resistance. Future large-scale, multicenter trials are needed to validate CD44 isoforms as prognostic biomarkers and therapeutic targets.