Sharp Increase in Expression of Subunit Genes and Activity of Proteasomes in Laringeal Ontogeny Is Associated with the Development of Squamous Cell Carcinoma

Abstract—Proteasomes, the most important participants in protein catabolism, maintain proteostasis and regulate cellular processes in ontogeny. Deviations in the functioning of proteasomes are associated with the development of various pathologies, including a number of oncological diseases. In this work, we studied changes in subunit gene expression and proteasome activity in laryngeal cancer tissue and epithelium of patients with chronic hyperplastic diseases of the larynx, which are considered obligate precancer. The activity of circulating proteasomes was also studied in the same groups of patients. The level of gene expression was assessed using quantitative reverse transcriptase followed by PCR in real time. A method for assessing chymotrypsin-like (CTL) and caspase-like (CL) activities of proteasomes has been modified for the analysis of small volumes of biopsy samples. An increase in the level of expression of the proteasome genes (PSMB6, PSMB7, PSMB5, and PSMB4) in the tissues of squamous cell carcinoma of the larynx was shown compared to pretumor samples. An increase in CTL and CL activities of intracellular proteasomes in the malignant epithelium of the larynx was also found in comparison with the conditionally normal tissue and with the epithelium of patients with chronic hyperplastic diseases of the larynx. An increase in chymotrypsin-like activity was observed in circulating proteasomes. ROC-analysis (Receiver operating characteristic) revealed the relationship between PSMB5 mRNA expression and CTL activity of tissue proteasomes with the development of laryngeal cancer in patients with chronic hyperplastic diseases of the larynx. In the future, it is possible to use these indicators to develop a method for predicting the transition of precancer of larynx to cancer.