Abstract
Introduction. A protein gankyrin, which was originally identified as a component of the 26S proteasome, is now of great importance. Gankyrin can function as an oncogene in various types of human cancers.
Aim. To examine the expression of gankyrin in colon tumors, in relation to the expression of transcription factors, growth factors and components of the AKT/mTOR signaling pathway.
Materials and methods. The study included 56 patients diagnosed with colorectal cancer aged 43 to 75 years (mean age 54 years). Patients received combined treatment, which included neoadjuvant chemotherapy according to the FOLFOX or XELOX scheme, and surgical resection of the affected area of the intestine performed in the clinics of the Research Institute of Oncology, Tomsk National Research Medical Center. Expression of gankyrin, transcription and growth factors, and components of the AKT/mTOR signaling pathway were determined by real-time PCR.
Results. In case of distant metastases, a 2.4-fold decrease in gankyrin expression was observed compared to patients with T1-2N0-2M0 stage cancer. Gankyrin expression was decreased 4.3- and 2.9-fold in highly differentiated tumors compared to moderately differentiated and low-differentiated tumors, respectively. In case of durable tumor growth stabilization, the level of gankyrin mRNA decreased 4.0-fold compared to patients with partial regression. There was a 3.2-; 5.2- and 41.0-fold increase in the expression of 70S 6 kinase, NF-kB p50 and PD-1 in patients with increased expression (> 1.0 CU) against a 51.1-fold decrease in VHL expression compared to patients with reduced gankyrin expression.
Conclusion. The study revealed features of expression of gankyrin, transcription factors, growth factors, AKT/mTOR signaling pathway components, receptors and ligands of programmed cell death, the degree of tumor differentiation, as well as tumor response to treatment.
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