Influence of neoadjuvant therapy on the expression of molecular markers in gastric cancer
https://doi.org/10.18027/2224-5057-2020-10-29-34
Abstract
Introduction. Gastric cancer remains the leading cause of death from malignant neoplasms. Its pathogenesis is known to be a multistage and heterogeneous process with a wide range of genetic changes. Among the leading mechanisms, the dysregulation of the most important signaling cell pathways is distinguished, which determines the disruption of the cell cycle, cell differentiation, DNA repair, and apoptosis processes and leads to the development of gastric cancer. This work aimed to study the expression of the AKT/mTOR and AMPK signaling pathway components after the FLOT chemotherapy in patients with gastric cancer.
Material and methods. The study includes 24 patients with gastric cancer. The patients received combined treatment, including neoadjuvant chemotherapy (FLOT) and surgical resection of the stomach. Specimen contained normal and tumor tissues obtained during diagnostic gastroscopy of patients. The mRNA level of the studied parameters was determined by real‑time PCR.
Results. Significant changes occurred when examining the level of indicators after treatment. Against the background of non‑adjuvant therapy, there was a decrease in 4EBP1 expression by 2.2 times compared to its level before surgery.
The effect of the treatment was associated with a set of indicators. They allow predicting the impact of therapy. There was a decrease in the expression of 4EBP, mTOR, and AMPK as the effect of treatment decreased in groups of patients with complete regression, partial regression, stabilization and progression of the disease.
Conclusion. A decrease in 4EBP1 expression was found in gastric cancer tissue under the influence of neoadjuvant therapy. Molecular markers that can predict the development of resistance to antitumor therapy are associated with the features of the AKT/mTOR signaling pathway. The initially high expression of AMPK, mTOR, and 4EBP1 is a key event mediating the development of the neoadjuvant therapy effect in gastric cancer.
Material and methods. The study includes 24 patients with gastric cancer. The patients received combined treatment, including neoadjuvant chemotherapy (FLOT) and surgical resection of the stomach. Specimen contained normal and tumor tissues obtained during diagnostic gastroscopy of patients. The mRNA level of the studied parameters was determined by real‑time PCR.
Results. Significant changes occurred when examining the level of indicators after treatment. Against the background of non‑adjuvant therapy, there was a decrease in 4EBP1 expression by 2.2 times compared to its level before surgery.
The effect of the treatment was associated with a set of indicators. They allow predicting the impact of therapy. There was a decrease in the expression of 4EBP, mTOR, and AMPK as the effect of treatment decreased in groups of patients with complete regression, partial regression, stabilization and progression of the disease.
Conclusion. A decrease in 4EBP1 expression was found in gastric cancer tissue under the influence of neoadjuvant therapy. Molecular markers that can predict the development of resistance to antitumor therapy are associated with the features of the AKT/mTOR signaling pathway. The initially high expression of AMPK, mTOR, and 4EBP1 is a key event mediating the development of the neoadjuvant therapy effect in gastric cancer.
About the Authors
L. V. Spirina
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical University
Russian Federation
Russian Federation
Liudmila V. Spirina, MD, PhD, DSc, Leader Researcher, Laboratory of Tumor Biochemistry, Tomsk National Research Medical Center of the Russian Academy of Sciences, Professor of the Department of Biochemistry and Molecular Biology with a Course in Clinical Laboratory Diagnostics, Siberian State Medical University
Tomsk
A. V. Avgustinovich
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
Aleksandra V. Avgustinovich, MD, PhD, Leader Researcher, Department of Abdominal Oncology
Tomsk
S. G. Afanasiev
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
Sergey G. Afanasiev, MD, PhD, DSc, Prof, Head of Department of Abdominal Oncology
Tomsk
M. Yu. Volkov
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
M. Yu. Volkov, MD, PhD, oncologist of Department of Abdominal Oncology
Tomsk
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Review
For citations:
Spirina L.V., Avgustinovich A.V., Afanasiev S.G., Volkov M.Yu. Influence of neoadjuvant therapy on the expression of molecular markers in gastric cancer. Malignant tumours. 2020;10(1):29‑34. (In Russ.) https://doi.org/10.18027/2224-5057-2020-10-29-34
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