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.

背景：口腔癌的治疗耐药仍是临床面临的重大挑战，其中癌症干细胞（cancer stem cells, CSCs）发挥着关键作用。作为核心的癌症干细胞标志物CD44（CD44），可通过药物外排、DNA修复及抗凋亡通路参与多药耐药机制。本荟萃分析旨在通过分析对照临床研究，系统评价口腔癌患者CD44表达水平与临床病理特征之间的关联。
方法：本研究系统检索了自建库至2022年9月的PubMed、EMBASE、Cochrane Library、Web of Science、中国知网（CNKI）、维普（VIP）、万方（WanFang）及中国生物医学文献数据库。纳入探讨口腔癌患者CD44过表达与临床病理特征及生存结局关系的对照临床研究。采用纽卡斯尔-渥太华量表（Newcastle-Ottawa Scale）进行质量评价，使用RevMan 5.3软件进行数据分析。
结果：最终纳入10项高质量研究，共包含846例口腔癌患者。分析显示，CD44过表达与局部肿瘤进展期（T分期：比值比[OR]=1.38；95%置信区间[CI]：1.14~1.66；P<0.001；异质性指数I²=25%）显著相关。未发现CD44过表达与N分期、组织学分级或血管侵犯存在显著关联。由于各研究报告方法存在异质性，合并生存分析的结果受限。
结论：CD44过表达可作为口腔癌治疗耐药的分子标志物，尤其与局部肿瘤进展密切相关。本研究结果提示，靶向CD44的治疗策略有望克服口腔癌的治疗耐药。未来需开展大规模多中心临床试验，以验证CD44亚型作为预后生物标志物及治疗靶点的价值。