Tear fluid as noninvasive liquid biopsy reveals proteins associated with malignant transformation of oral lesions
Santos, E. S.; Granato, D. C.; Carnielli, C. M.; de Figueiredo, D.; Trino, L. D.; Patroni, F. M. S.; Pauletti, B. A.; Domingues, R. R.; Sa, J.; Normando, A. G. C.; Daher, N.; Kravchenko-Balasha, N.; Debasis, P.; Minghim, R.; Kowalski, L. P.; Santos-Silva, A. R.; Lopes, M. A.; Brandao, T. B.; Prado-Ribeiro, A. C.; Leme, A. F. P.
Show 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.
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