Risk assessment of oral leukoplakia malignant transformation based on the ubiquitin-proteasome system indicators

Abstract

Relevance. The ubiquitin-proteasome system controls the activity and stability of various cellular proteins that affect cellular homeostasis by the regulation of signalling cascades. The system activity is associated with the onset and progression of oral squamous cell carcinoma, as the system participates in the specific proteolysis of most intracellular proteins involved in cancer pathogenesis.Material and methods. The study included 61 patients (28 men and 33 women) aged 21 to 75 y.o. The study determined chymotrypsin-like (CTL) and caspase-like (CL) activities of circulating and intracellular proteasomes in blood serum and biopsy specimens taken from the oral mucosa by hydrolysis of the corresponding fluorogenic oligopeptide on a «Cytation1» multi-mode microplate reader-imager at an excitation wavelength of 360 nm and an emission of 460 nm, the specific activity of the proteasomes was expressed in units of activity.Results. The value of the specific chymotrypsin-like activity of circulating proteasomes in non-homogeneous leukoplakia and oral squamous cell carcinoma was 1.76 (p < 0.001) times and 2.27 (p < 0.001) times higher relative to the comparison group. Pairwise comparison of signs showed a statistically significant difference in chymotrypsinlike activity between the groups of non-homogeneous and homogeneous leukoplakia (p < 0.001), non-homogeneous leukoplakia and oral squamous cell carcinoma (p = 0.04). The values of specific chymotrypsin-like and caspase-like activities of intracellular proteasomes in biopsy specimens taken from the pathological focus in the groups of homogeneous, non-homogeneous leukoplakia and squamous cell carcinoma of the oral cavity were 1.6, 2.38, 3 (p = 0.002, p = 0.004, p = 0.03) and 1.5, 2.8 and 3.3 (p = 0.003, p = 0.012, p < 0.001) times higher compared to the control group.Conclusion. The proposed logit model for risk assessment of oral leukoplakia malignant transformation, based on the indicators of the ubiquitin-proteasome system, can improve the quality of diagnosis.