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

Int J Mol Sci. 2021 Oct 16;22(20):11176. doi: 10.3390/ijms222011176.

Abstract

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.

Keywords: AKT/mTOR component; LC3B; PD-L1; gastric cancers; growth factors; transcriptional factors.

MeSH terms

  • Adult
  • Autophagy
  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Microtubule-Associated Proteins / metabolism*
  • Middle Aged
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism
  • Programmed Cell Death 1 Receptor / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / metabolism*
  • TOR Serine-Threonine Kinases / metabolism*
  • Transcription Factors / metabolism*
  • Young Adult

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Intercellular Signaling Peptides and Proteins
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • PDCD1 protein, human
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • Transcription Factors
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases