Abstract 7062: Potential biomarker role of LCN2, MMP9 and LCN2/MMP9 complex in OSCC

Abstract Background: Oral Squamous Cell Carcinoma (OSCC) is considered as a major morbidity and mortality in LMICs, with five-year survival rate of less than 50%. Limited availability of early diagnostic markers is one of the important causes of this abysmal outcome. We identified 135 differentially regulated candidate proteins using LC/MS-based shotgun proteomics in the saliva of OSCC patients, of which LCN2 and MMP9 were also found to be significantly upregulated. Dysregulated levels of LCN2, MMP9, and LCN2/MMP9 complex have also been reported in OSCC. To establish the potential role as biomarkers, we evaluated them in OSCC patients. Methodology: 356 biopsy-proven treatment-naïve OSCC, 26 Oral Pre-Malignant Diseases (OPMDs) and 118 healthy subjects were recruited for the study. 5 ml of unstimulated saliva and 3 ml of whole blood were collected at baseline and during follow-ups. Salivary and serum levels of LCN2, MMP9 and LCN2/ MMP9 complex were estimated using sandwich ELISA. The levels were analysed in various groups and were also correlated with the therapy response and the disease outcome. Results: Significantly higher (p≤0.0001) levels of LCN2 in saliva and serum (median- 609.15ng/ml & 186.18ng/ml) of patients compared to OPMD (median-358.47ng/ml & 124.05ng/ml) and healthy controls (median-95.70ng/ml & 85.53ng/ml) respectively. Salivary and serum levels of MMP9 (median-194.03ng/ml & 3476.755ng/ml) were also found to be significantly higher (p≤0.0001) than their levels in OPMD (median-206.50ng/ml & 404.08ng/ml) and control group (median-188.05ng/ml & 540.18ng/ml) respectively. Also, the level of complex of LCN2/MMP9 in saliva and serum (median-145.65ng/ml, median-94.37 ng/ml) was observed to be significantly higher (p≤0.0001) than OPMD (median-90.66ng/ml & 55.20ng/ml) and healthy controls (median-70.88ng/ml & 52.76ng/ml) respectively. The increased level of these proteins also correlated with staging and was also found to have a decreasing trend with successful therapy. On ROC analysis, for identifying the ability as a diagnostic marker, significant AUCs for LCN2 in saliva and serum of patients compared to healthy controls were found (0.7446 & 0.6802) with a sensitivity of (88.64% & 77.25%) and specificity of (60.17% & 60.17%) respectively. For MMP9, the AUC for serum was significant (0.9326), with a sensitivity of 85.01% and specificity of 95.54%. AUC for LCN2/MMP9 complex for saliva and serum were also found to be significant (0.7415 & 0.7266) with a sensitivity of (86.74% & 78.80%) and specificity of (52.54% & 63.56%) respectively. Survival curve analysis revealed that pretreatment salivary LCN2 can be used as a predictive marker for OS of OSCC patients with an HR of 1.915 (CI 1.173 to 3.127) and salivary levels of MMP9 for DFS with HR of 2.823 (CI 0.9813 to 8.122). Conclusion: Baseline LCN2, MMP9, and LCN2/MMP9 complex can be used as potential biomarkers for the diagnosis and prognostication of patients with OSCC. Citation Format: Smriti Suri, Sushmita Ghoshal, Jaimanti Bakshi, Arnab Pal. Potential biomarker role of LCN2, MMP9 and LCN2/MMP9 complex in OSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7062.