AKT/mTOR Signal Cascade and Expression of PD-1, PD-L1, and PD-L2 in Gastric Cancer
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Cascade and Expression of PD-1, PD-L1, and PD-L2 in Gastric Cancer
L. V. Spirina1,2, A. V. Avgustinovich1, S. G. Afanas’ev1, I. V. Kondakova1, M. Yu. Volkov1, A. Yu. Dobrodeev1, and A. I. Boronkina2 Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 170, No. 7, pp. 91-95, July, 2020 Original article submitted April 21, 2020 The peculiarities of gastric cancer development associated with the expression levels of components of the AKT/mTOR signaling cascade and PD, PD-L1, PD-L2 have not yet been identified. We revealed the fundamental changes in the expression AKT/mTOR and PD receptors and their ligands associated with dissemination of gastric cancer. An increase in the mRNA level of all components of this cascade was demonstrated. The expression of mTOR and AKT decreased against the background of enhanced expression of PTEN phosphatase. The increase in the expression of PD-1 receptors and PD-L1 and PD-L2 ligands was most pronounced in patients with distant metastases. Key Words: gastric cancer; AKT/mTOR signaling cascade; PD; PD-L1; PD-L2 The AKT/mTOR cascade hyperactivation is a wellknown molecular event in carcinogenesis. It participates in cell proliferation, metabolism, growth, migration, and angiogenesis [2,6]. It is presented by the key kinases AKT and mTOR in the complexes mTORC1 and mTORC2. mTORC1 regulates cell growth and proliferation via stimulation of anabolic processes (biosynthesis of protein, lipids, and organelles) and also limits autophagy [1]. The function mTORC2 is not comprehensively studied. It can participate in mTORC2-AKT signaling in cancer cells and can affect T-cell activity by regulating the expression of programmed death-1 receptors (PD-1) and their ligands PD-L1, PD-L2 [3] Diagnosis and treatment of gastric cancer (GC) remains a complex problem in modern oncology. Hyperactivation of the AKT/mTOR signaling cascade is associated with many malignant neoplasms, including GC [7]. There are data that the expression of phosphorylated form of AKT is associated with the prognosis of the disease and with the effectiveness of 1 Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, Russia; 2Siberian State Medical University, Ministry of Health of the Russian Federation, Tomsk, Russia. Address for correspondence: [email protected]. L. V. Spirina
therapy [4]. The components of the AKT/mTOR signaling pathway are now considered as markers for GC diagnosis [5]. Immune drugs (PD receptor blockers) are registered as antitumor drugs for this pathology. However, some peculiarities of the development and course of the diseases associated with the expression level of the components of the AKT/mTOR signaling pathway and PD, PD-L1, PD-L2 remain unclear. Our aim was to evaluate the expression of the components of the AKT/mTOR signaling cascade and expression of PD, PD-L1, PD-L2 in patients with GC depending on the dissemination of the tumor process.
MATERIALS AND METHODS The study included 38 patients with GC. Combined treatment consisted of neoadjuvant FOLFOX6 or FLOT
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