Lipid droplets’ functional protein caveolin-2 is associated with lipid metabolism-related molecule FABP5 and EMT marker E-cadherin in oral epithelial dysplasia

Abstract

Abstract Background: The function of lipid droplets (LDs) has not been clarified in precancerous lesions, and the relationship between LDs, lipid metabolism, and epithelial-mesenchymal transition (EMT) remains unclear in the carcinogenesis processes in the oral cavity.Methods: Tissue frozen sections were collected for oil red O staining of LDs. Forty-eight oral squamous cell carcinomas (OSCC), 78 oral potentially malignant disorders (OPMDs), and 25 normal paraffin-embedded tissue sections were included to explore the LDs surface protein caveolin-2 and perilipin-3, lipid metabolism-related molecule fatty acid binding protein 5 (FABP5), and EMT biomarker E-cadherin expression by immunohistochemical staining. Results: The accumulation of LDs was observed in OPMDs and OSCCs compared to normal tissues (P < 0.05). In general, an increasing trend of caveolin-2, perilipin-3, and FABP5 expression was detected from the normal to OPMDs to OSCC groups (P < 0.05); however, the increased level of perilipin-3 was not significant in OPMDs compared to the normal controls (P > 0.05). In addition, caveolin-2, perilipin-3, and FABP5 expression were positively correlated with epithelial dysplasia in OPMDs, whereas E-cadherin positivity was negatively correlated with epithelial dysplasia and histopathological grade in OPMDs and OSCC, respectively. A negative correlation of caveolin-2 (P < 0.01, r = - 0.1739), and FABP5 (P < 0.01, r = - 0.1880) with E-cadherin expression was detected. The caveolin-2 (P < 0.0001, r = 0.2641) and perilipin-3 (P < 0.05, r = 0.1408) staining was positively correlated with FABP5. OSCC local recurrence was associated with high expression of caveolin-2 (P < 0.05) and FABP5 (P < 0.05), and lymph node metastasis was associated with high FABP5 expression (P < 0.05) but low E-cadherin expression (P < 0.05). The caveolin-2 high expression group had a worse disease-free survival (DFS) (P < 0.05). Conclusion: In the oral epithelial carcinogenesis process, LDs begin to accumulate early in the precancerous stage. LDs may be the regulator of FABP5-associated lipid metabolism and are closely related to the process of EMT; caveolin-2 could be the main functional protein, indicating that caveolin-2 is a potential biomarker for oral carcinogenesis and prognosis.