Genetic analysis of Mixed Lineage Kinase domain-like pseudokinase (MLKL) in Oral Squamous Cell Carcinoma: A Comparative Evaluation between Young and Old patients.

Abstract

Background: Oral squamous cell carcinoma (OSCC) is characterized by dysregulation of multiple cell signaling pathways, including the necroptotic pathway. Recently, the incidence of OSCC is increasing among the young population (below the age of 40 years). These patients exhibit differences in the pathobiological characteristics and treatment response compared to the older cohorts. There is a notable lack of research exploring the role of necroptotic proteins in younger OSCC patients.

Aim: To investigate the expression of Mixed Lineage Kinase domain Like Pseudokinase (MLKL), a key necroptotic protein, in young and old patients with OSCC.

Methodology: The study included sixty histopathologically confirmed cases of OSCC, categorized into two groups; Group I - 30 patients aged > 40 years and Group II - 30 patients aged ≤ 40 years. Each of these groups consisted of 10 cases each of well differentiated, moderately differentiated and poorly differentiated OSCC. The samples were evaluated for the MLKL gene expression using Real time PCR and the results were analyzed using the 2-ΔΔCT method.

Results: The real-time PCR analysis showed a 31% decrease in MLKL gene expression in the younger age group (Group II) compared to the older group. A decrease of 40% in WDSCC, 67% in MDSCC, and 38% in PDSCC was observed in the younger group compared to the older age group.

Conclusion: Our findings suggest age-related differences in necroptotic cell death regulation through MLKL, with decreased MLKL expression observed in younger patients compared to older patients. Modulating necroptotic cell death pathways in OSCC can promote switching between different cell death pathways and provide effective therapeutic strategies.