Tear fluid as noninvasive liquid biopsy reveals proteins associated with malignant transformation of oral lesions

Abstract

Oral leukoplakias (OLs) are premalignant lesions that can progress into oral squamous cell carcinoma (OSCC). This study hypothesized that tear fluid, as a noninvasive biofluid, reflects proteomic alterations associated with malignant transformation. The tear proteome of 44 individuals, including healthy controls, OL/PVL (proliferative verrucous leukoplakia), and OSCC patients, was deeply profiled, revealing 828 protein groups clustered according to histopathological alterations. N-glycoproteome analysis identified immune-related proteins, while public RNA-seq integration indicated immune imbalance marked by increased B-cell and decreased macrophage signatures during disease progression. Several immune-associated proteins and epithelial markers, including desmoplakin, KRT14, and DSC1, emerged as potential indicators of malignant transformation. These findings demonstrate that tear fluid reflects oral carcinogenic processes, thereby serving as a noninvasive liquid biopsy for early detection and clinical monitoring.