Smac/DIABLO protein acts as an independent prognostic factor in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) poses significant health risks with increasing incidence and mortality rates. In this context, there is an urgent need to explore novel biomarkers to enhance therapeutic strategies and improve survival. Understanding apoptotic evasion in cancer pathogenesis, this pioneering study aims to investigate the correlation between a pro-apoptotic protein Smac/DIABLO and patient prognosis within the OSCC cohort. Immunohistochemistry (IHC) was employed to analyze Smac/DIABLO protein expression and correlate with clinicopathological and prognostic factors during a long-term follow-up. Smac/DIABLO low expression was associated with worse overall survival (OS), relapse-free survival (RFS), disease-specific survival (DSS), and an increase in risk of lymph node metastasis (LNM) in univariate analyses. Furthermore, multivariate analyses confirmed Smac/DIABLO as an independent prognostic factor, predicting poorer OS [Hazard Ratio (HR) = 3.6 (95% CI 1.7–7.6), p < 0.001], RFS [HR = 2.9 (95% CI 1.4–5.6), p = 0.003], DSS [HR = 6.7 (95% CI 2.7–16.7), p < 0.001], and increased likelihood of LNM [Odds Ratio (OR) = 4.8 (95% CI 1.4–15.9), p = 0.011]. Patients with positive Smac/DIABLO expression exhibited three times higher survival probability. Low proapoptotic protein Smac/DIABLO expression significantly influences prognostic predictions and strongly correlates with poor OSCC outcomes. Future studies involving Smac-mimetic drugs in OSCC are needed to evaluate their pro-apoptotic potential in cancer cells.