Objective: To evaluate the degree of current evidence through a systematic review and meta-analysis on the association between podoplanin overexpression and the malignant transformation of oral potentially malignant disorders (OPMDs). Methods: A systematic search was performed in the MEDLINE (through PubMed), Embase, Scopus, and Web of Science databases for primary-level research published before December 2024, strictly designed as longitudinal cohorts with follow up data, and no restrictions by language or publication date. The Quality in Prognosis Studies QUIPS tool (developed by the Cochrane Prognosis Methods Group) was applied in order to assess the methodological quality and risk of bias. Meta-analyses, subgroup meta-analyses, sensitivity, and small-study effects analyses were performed. Results: Twelve primary-level studies met the eligibility criteria and were included, which followed up 857 OPMDs patients over time. Podoplanin overexpression was significantly associated with an increased risk of the malignant transformation of OPMDs (RR = 3.64, 95% CI = 2.18–6.10,p< 0.001). Podoplanin also proved to be a valuable biomarker in the malignant transformation of all investigated OPMDs (oral leukoplakia:p< 0.001; erythroplakia:p= 0.05; oral lichen planus:p= 0.02; discoid lupus erythematosus:p= 0.009). In addition, podoplanin overexpression was significantly associated with an increased risk of cancer development in several study subgroups with methodological implications (anti-podoplanin D2-40 antibody:p< 0.001; membrane and cytoplasm staining:p< 0.001; antibody dilution at 1:100:p< 0.001; overnight incubation:p< 0.001; 4 °C incubation:p< 0.001; cut-off point > 1%:p< 0.001; low risk of bias:p< 0.001). Conclusions: This systematic review and meta-analysis, on the basis of the evidence, indicates that podoplanin overexpression is a predictor of an increased risk of malignant transformation in OPMDs, singularly in oral leukoplakias. Its evaluation using immunohistochemical methods would be advisable in pathology laboratories.
目的：通过系统综述和荟萃分析，评估足萼蛋白过表达与口腔潜在恶性疾患（OPMDs）恶性转化之间关联的现有证据强度。方法：系统检索MEDLINE（通过PubMed）、Embase、Scopus和Web of Science数据库中截至2024年12月发表的原发性研究，严格筛选为具有随访数据的纵向队列研究，不限制语言或发表日期。采用预后研究质量QUIPS工具（由Cochrane预后方法组制定）评估方法学质量和偏倚风险。进行了荟萃分析、亚组荟萃分析、敏感性分析及小样本效应分析。结果：共纳入12项符合条件的一级研究，共随访857名OPMDs患者。足萼蛋白过表达与OPMDs恶性转化风险增加显著相关（RR = 3.64，95% CI = 2.18–6.10，p < 0.001）。足萼蛋白在所有研究的OPMDs恶性转化中均被证明是有效的生物标志物（口腔白斑：p < 0.001；红斑：p = 0.05；口腔扁平苔藓：p = 0.02；盘状红斑狼疮：p = 0.009）。此外，在多个具有方法学意义的亚组分析中，足萼蛋白过表达均与癌症发生风险增加显著相关（抗足萼蛋白D2-40抗体：p < 0.001；膜与细胞质染色：p < 0.001；抗体稀释度1:100：p < 0.001；过夜孵育：p < 0.001；4°C孵育：p < 0.001；截断值>1%：p < 0.001；低偏倚风险：p < 0.001）。结论：本系统综述和荟萃分析基于现有证据表明，足萼蛋白过表达是OPMDs（尤其是口腔白斑）恶性转化风险增加的预测因子。建议病理实验室采用免疫组化方法对其进行评估。
肿瘤(癌症)患者之家