Análisis de la actividad de las catepsinas en saliva en el carcinoma epidermoide de faringe y laringe

Resumen

Introduction and objectives: An observational case-control study aimed to demonstrate differences in cathepsin activity in the saliva of patients affected by pharyngeal or laryngeal squamous cell carcinoma compared to a healthy population. Additionally, we sought to establish a valid cathepsin activity cutoff point related to cancer diagnosis and poor prognostic factors. Methods: We selected two groups: patients with P16-negative pharyngeal and laryngeal squamous cell carcinoma (cases) and healthy volunteers without upper airway diseases (controls). Saliva samples were collected from both groups, along with relevant epidemiological and clinical variables. Results: We conducted protein profiles based on activity using fluorescent probes specific for cathepsins B, L, S, and X/Z. Fourteen two-dimensional polyacrylamide gels were subjected to SDS-PAGE analysis, analyzing 108 saliva samples (76 from the case group and 32 from the control group). Optical density intensity data were collected for the different cathepsins. The median optical density intensity values were as follows:• Cathepsin B: 191.3 (range: 77.6-336.5). • Cathepsin S: 432.8 (range: 232.9-899.6). • Cathepsin L: 68.8 (range: 21.7-200.9).differences were found between the case group and the control group for cathepsin S activity (p<0.01) and cathepsin L activity (p<0.01), but not for cathepsin B activity (p>0.99). Using cathepsin S activity levels, we constructed a receiver operating characteristic (ROC) curve for diagnosing squamous cell carcinoma, establishing a cutoff point at an activity level of 479.7. Multivariate analysis demonstrated significant differences in cathepsin S activity between the two groups (p<0.03). We also generated ROC curves using cathepsin S activity data to predict: • Advanced primary tumor size (cT and pT). • Presence of cervical lymph node metastasis (cN and pN). • Advanced tumor stage (clinical and pathological). Differences in cathepsin S activity were observed among patients with advanced primary tumors (p<0.02) and advanced tumor stages (p<0.01) compared to those with initial stages. However, no significant differences were found between N+ and N0 patients (p<0.43). Finally, we designed ROC curves using cathepsin S activity as a predictive marker for postoperative complications and salivary fistula in total laryngectomy patients. Unfortunately, no significant differences were demonstrated in either case (p<0.21 for overall complications and p<0.16 for salivary fistula). Conclusions: Salivary cathepsin S activity is elevated in patients with pharyngeal and laryngeal squamous cell carcinoma compared to healthy individuals, while cathepsin L activity is decreased. Cathepsin S activity can serve as a diagnostic tool for squamous cell carcinoma and as a predictor of advanced primary tumors or tumor stages. However, it cannot be used as a predictive marker for cervical lymph node metastasis or postoperative complications. Notably, no relevant X/Z cathepsin activity was detected. Significant