搜索与口腔白斑恶性转化相关的生物标志物对于口腔癌患者的早期诊断和改善预后至关重要。本系统性综述和荟萃分析的目的是评估与口腔白斑恶性转化潜在相关的蛋白质标记物。搜索了五个数据库和灰色文献。总共，包括了142项研究进行定性综合，其中因其在口腔白斑 (OL) 至口腔鳞癌 (OSCC) 恶性进展中的潜在作用而调查了173种蛋白质。这些蛋白质的丰度主要通过免疫组化和 ELISA 分析固定组织和/或生物流体样本，并且其中有12个样本共享。富集分析表明，差异丰度蛋白主要涉及细胞死亡调节、细胞增殖调节和凋亡过程调节。此外，这些蛋白质主要表达于细胞外区域 (55.5%)、细胞表面 (24.8%) 和囊泡 (49.1%)。荟萃分析显示，肿瘤进展相关的蛋白质 PD-L1、Mdm2和粘液蛋白-4 在OSCC患者中显著与更高的丰度相关，其 Odds Ratio (OR) 分别为0.12 (95% CI: 0.04- 0.40)、0.44 (95% CI: 0.24-0.81) 和 0.18 (95% CI: 0.04-0.86)，证据程度适中。结果表明，已经在OSCC的起始和进展中调查了一组蛋白质，其转录表达与与预后和侵袭相关的临床特征有关。强烈建议对此生物标志物组进行进一步的验证和验证，以用于未来的临床应用。©2023年Normando，dos Santos，Sá，Busso-Lopes，De Rossi，Patroni，Granato，Guerra，Santos-Silva，Lopes和Paes Leme。

The search for biomarkers associated with oral leukoplakia malignant transformation is critical for early diagnosis and improved prognosis of oral cancer patients. This systematic review and meta-analysis aimed to assess protein-based markers potentially associated with malignant transformation of oral leukoplakia. Five database and the grey literature were searched. In total, 142 studies were included for qualitative synthesis, where 173 proteins were investigated due to their potential role in malignant progression from oral leukoplakia (OL) to oral squamous cell carcinoma (OSCC). The abundance of these proteins was analyzed in fixed tissues and/or biofluid samples, mainly by immunohistochemistry and ELISA, and 12 were shared by both samples. Enrichment analysis revealed that the differential abundant proteins are mostly involved with regulation of cell death, regulation of cell proliferation, and regulation of apoptotic process. Also, these proteins are mainly expressed in the extracellular region (55.5%), cell surface (24.8%), and vesicles (49.1%). The meta-analysis revealed that the proteins related to tumor progression, PD-L1, Mdm2, and Mucin-4 were significantly associated with greater abundance in OSCC patients, with an Odds Ratio (OR) of 0.12 (95% CI: 0.04-0.40), 0.44 (95% CI: 0.24-0.81), and 0.18 (95% CI: 0.04-0.86), respectively, with a moderate certainty of evidence. The results indicate a set of proteins that have been investigated across OSCC initiation and progression, and whose transcriptional expression is associated with clinical characteristics relevant to the prognosis and aggressiveness. Further verification and validation of this biomarkers set are strongly recommended for future clinical application.© 2023 Normando, dos Santos, Sá, Busso-Lopes, De Rossi, Patroni, Granato, Guerra, Santos-Silva, Lopes and Paes Leme.