Abstract P41: Potential role of LCN2, MMP9 and LCN2/MMP9 complex as plausible biomarkers of Oral Squamous Cell Carcinoma (OSCC)

Abstract Background: OSCC is a significant health problem in LMICs including India, and has poor outcome due to lack of diagnostic marker. We identified 135 dysregulated candidate proteins in the saliva of OSCC patients using LCMS, of which Lipocalin 2(LCN2) and Matrix Metalloproteinase 9(MMP9) were significantly upregulated. We explored the potential role of these proteins as probable biomarker in OSCC. Methodology: 351 OSCC,26 OPMDs and 118 healthy controls were recruited.5ml unstimulated saliva and 3ml blood were collected at baseline and during follow-ups. Protein levels were measured by sandwich ELISA, and analysed using appropriate statistical tests. Results: LCN2 was significantly higher( p≤0.0001 )in saliva and serum(median-609.15ng/ml & 186.18ng/ml)of patients compared to OPMD(median-358.47ng/ml & 124.05ng/ml)and controls(median-95.70ng/ml & 85.53ng/ml).Salivary and serum levels of MMP9(median-194.03ng/ml & 3476.755ng/ml)were significantly higher( p≤0.0001 )than in OPMD(median-206.50ng/ml & 404.08ng/ml)and controls (median-188.05ng/ml & 540.18ng/ml)respectively.LCN2/MMP9 complex in saliva and serum(median-145.65ng/ml,median-94.37 ng/ml)was also significantly higher( p≤0.0001 )than OPMD(median-90.66ng/ml & 55.20ng/ml)and controls(median-70.88ng/ml & 52.76ng/ml)respectively. During follow-ups post-therapy, there was a significant decrease in the level of these proteins. ROC analysis revealed a significant AUCs for LCN2 in saliva and serum of patients compared to healthy controls(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 significant(0.7415 & 0.7266)with a sensitivity of(86.74% & 78.80%)and specificity of(52.54% & 63.56%)respectively. Combining the three proteins using multiple logistic regression a risk prediction model was generated, with a better(p<0.0001)AUC of(0.8025 & 0.9369). Survival curve analysis revealed that pretreatment salivary LCN2 and salivary levels of MMP9 can be used as a predictive marker for OS(HR of 1.915 CI 1.173 to 3.127)and DFS(HR of 2.823 CI 0.9813 to 8.122)respectively. Conclusion: Baseline LCN2, MMP9 and LCN2/MMP9 complex can be used as potential biomarkers for the diagnosis and prognostication of patients of OSCC. Citation Format: Smriti Suri, Himanshu Garg, Sushmita Ghoshal, Jaimanti Bakshi, Arnab Pal. Potential role of LCN2, MMP9 and LCN2/MMP9 complex as plausible biomarkers of Oral Squamous Cell Carcinoma (OSCC) [abstract]. In: Proceedings of Frontiers in Cancer Science 2025; 2025 Nov 5-7; Singapore. Philadelphia (PA): AACR; Cancer Res 2026;86(13_Suppl):Abstract nr P41.