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PD-L1 Status in Gastric Cancers, Association with the Transcriptional, Growth Factors, AKT/mTOR Components Change, and Autophagy Initiation

Introduction: The programmed death receptor ligand 1 (PD-L1) immunohistochemistry (IHC) assay is a widely used selection method for pembrolizumab treatment in gastric cancer (GC) patients. PD-L1 is the main regulator of immunity in oncogenesis. Material and methods: The study included 38 patients wi...

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Autores principales: Spirina, Liudmila, Avgustinovich, Alexandra, Afanas’ev, Sergei, Volkov, Maxim, Dobrodeev, Alexey, Cheremisina, Olga, Kostromitsky, Dmitry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539424/
https://www.ncbi.nlm.nih.gov/pubmed/34681840
http://dx.doi.org/10.3390/ijms222011176
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author Spirina, Liudmila
Avgustinovich, Alexandra
Afanas’ev, Sergei
Volkov, Maxim
Dobrodeev, Alexey
Cheremisina, Olga
Kostromitsky, Dmitry
author_facet Spirina, Liudmila
Avgustinovich, Alexandra
Afanas’ev, Sergei
Volkov, Maxim
Dobrodeev, Alexey
Cheremisina, Olga
Kostromitsky, Dmitry
author_sort Spirina, Liudmila
collection PubMed
description Introduction: The programmed death receptor ligand 1 (PD-L1) immunohistochemistry (IHC) assay is a widely used selection method for pembrolizumab treatment in gastric cancer (GC) patients. PD-L1 is the main regulator of immunity in oncogenesis. Material and methods: The study included 38 patients with GC. The combined treatment consisted of neoadjuvant FOLFOX6, or FLOT, chemotherapy and surgery. PD-L1 + tumor status was recorded in 12 patients (CPS > 5), with a negative status recorded in 26 patients. RT-PCR determined the expression of molecular markers. The level of LC3B protein was detected by Western Blotting analysis. Results: An overexpression of PD-1, PD-L2 in the tumor is associated with AKT/mTOR mRNA profile change and autophagy initiation in IHC PD-L1 positive GCs. NACT influences these biological features, modifying the expression of AKT/mTOR components and autophagic flux. In PD-L1 positive cancers, the effect of NACT and molecular markers rearrangements are essential compared to the PD-L1 negative cancers. Conclusion: The IHC PD-L1 status in gastric cancers is the significant marker of cancer progression, recovering the multiple inner mechanisms of cancer spreading and leading to ineffective therapy. Autophagy induction and angiogenesis are found in PD-L1 positive gastric cancers.
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spelling pubmed-85394242021-10-24 PD-L1 Status in Gastric Cancers, Association with the Transcriptional, Growth Factors, AKT/mTOR Components Change, and Autophagy Initiation Spirina, Liudmila Avgustinovich, Alexandra Afanas’ev, Sergei Volkov, Maxim Dobrodeev, Alexey Cheremisina, Olga Kostromitsky, Dmitry Int J Mol Sci Article Introduction: The programmed death receptor ligand 1 (PD-L1) immunohistochemistry (IHC) assay is a widely used selection method for pembrolizumab treatment in gastric cancer (GC) patients. PD-L1 is the main regulator of immunity in oncogenesis. Material and methods: The study included 38 patients with GC. The combined treatment consisted of neoadjuvant FOLFOX6, or FLOT, chemotherapy and surgery. PD-L1 + tumor status was recorded in 12 patients (CPS > 5), with a negative status recorded in 26 patients. RT-PCR determined the expression of molecular markers. The level of LC3B protein was detected by Western Blotting analysis. Results: An overexpression of PD-1, PD-L2 in the tumor is associated with AKT/mTOR mRNA profile change and autophagy initiation in IHC PD-L1 positive GCs. NACT influences these biological features, modifying the expression of AKT/mTOR components and autophagic flux. In PD-L1 positive cancers, the effect of NACT and molecular markers rearrangements are essential compared to the PD-L1 negative cancers. Conclusion: The IHC PD-L1 status in gastric cancers is the significant marker of cancer progression, recovering the multiple inner mechanisms of cancer spreading and leading to ineffective therapy. Autophagy induction and angiogenesis are found in PD-L1 positive gastric cancers. MDPI 2021-10-16 /pmc/articles/PMC8539424/ /pubmed/34681840 http://dx.doi.org/10.3390/ijms222011176 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Spirina, Liudmila
Avgustinovich, Alexandra
Afanas’ev, Sergei
Volkov, Maxim
Dobrodeev, Alexey
Cheremisina, Olga
Kostromitsky, Dmitry
PD-L1 Status in Gastric Cancers, Association with the Transcriptional, Growth Factors, AKT/mTOR Components Change, and Autophagy Initiation
title PD-L1 Status in Gastric Cancers, Association with the Transcriptional, Growth Factors, AKT/mTOR Components Change, and Autophagy Initiation
title_full PD-L1 Status in Gastric Cancers, Association with the Transcriptional, Growth Factors, AKT/mTOR Components Change, and Autophagy Initiation
title_fullStr PD-L1 Status in Gastric Cancers, Association with the Transcriptional, Growth Factors, AKT/mTOR Components Change, and Autophagy Initiation
title_full_unstemmed PD-L1 Status in Gastric Cancers, Association with the Transcriptional, Growth Factors, AKT/mTOR Components Change, and Autophagy Initiation
title_short PD-L1 Status in Gastric Cancers, Association with the Transcriptional, Growth Factors, AKT/mTOR Components Change, and Autophagy Initiation
title_sort pd-l1 status in gastric cancers, association with the transcriptional, growth factors, akt/mtor components change, and autophagy initiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539424/
https://www.ncbi.nlm.nih.gov/pubmed/34681840
http://dx.doi.org/10.3390/ijms222011176
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