Exploring the biomarker potential of LCN2 and MMP9 proteins in Head and Neck Squamous Cell Carcinoma

Head and Neck Squamous Cell Carcinoma (HNSCC) is a major cancer-related health problem in low-and-middle-income countries (LMICs). A significant number of HNSCC cases result in overall poor disease outcomes, majorly attributed to late diagnosis due to the unavailability of suitable biomarkers. In one of our previous studies, a number of dysregulated proteins were identified using salivary proteomics in HNSCC patients; Lipocalin2(LCN2) and Matrix Metalloproteinase 9(MMP9) were among the topmost upregulated candidates. In this current prospective case–control study, we explored the clinical utility of these proteins in 351 biopsy-proven treatment-naïve HNSCC patients analysing their saliva, serum and tumour tissue. We compared them with 26 Oral Premalignant Diseases (OPMDs) and 118 healthy controls. The protein levels were estimated by Sandwich ELISA in saliva and serum and by Immunohistochemistry (IHC) and Immunofluorescence (IF) in tumour tissue. The findings were clinically correlated; Receiver Operating Characteristic (ROC) curves and survival curves were analysed to predict probable biomarker efficacy. The outcomes of the study were compared with The Cancer Genome Atlas (TCGA) database. The effect of their knockdown (KD) on cancer hallmarks was also studied in HNSCC cell lines. Collectively, our data demonstrate that baseline LCN2, MMP9, and the LCN2/MMP9 complex can be used as potential biomarkers for the diagnosis and prognostication of HNSCC patients.