Prognostic significance of AKT/mTOR signaling pathway components, transcription factors, and growth factors in the development of skin melanoma recurrence

Purpose of the study. Was to investigate the prognostic significance of the AKT/mTOR signaling pathway components, transcription, and growth factors in the development of skin melanoma recurrence.

Patients and methods. The study included 48 patients with a verified diagnosis of skin melanoma. All patients had a negative status for the BRAFV600E mutation. The study material consisted of samples of tumor and unchanged skin located at a distance of at least 1 cm from the tumor border, obtained during surgical treatment, which were frozen and stored at a temperature of –80 °C after sampling. Gene expression was assessed by real-time PCR. The status of the BRAF gene was assessed using allele-specific PCR. Statistical processing was carried out using the Statistica 12.0 software package.

Results. Predicting the course of cancer is an important task in practical oncology. The unfavorable outcome of melanomas is largely due to the tendency to relapses and metastasis in both the short and long-term follow-up period. While analyzing the study results, we noted the association of AKT/mTOR signaling pathway components with the development of skin melanoma recurrence and disease progression. It was revealed that the expression level of AKT, c-RAF, GSK‑3β and VEGFR2 is associated with an unfavorable outcome of the disease. A logistic regression model is presented that can accurately predict the risk of recurrence, taking into account the expression of protein kinase mTOR and the size of the tumor (T). The lack of significant indicators related to the biological features of the skin tumor does not allow to increase the effectiveness of treatment of such patients. Therefore, the attention of researchers is focused on finding optimal models for predicting the risk of an unfavorable outcome of the disease.

Conclusion. Molecular markers were identified that make it possible to predict an unfavorable outcome of the disease during the study. A logistic model based on the expression of the key mTOR kinase and the size of the T has been developed, which makes it possible to assess the risk of disease recurrence and change treatment tactics in a timely manner.

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