PRC1 plays an important role in lung adenocarcinoma and is potentially targeted by fostamatinib

Eur Rev Med Pharmacol Sci. 2022 Dec;26(23):8924-8934. doi: 10.26355/eurrev_202212_30567.

Abstract

Objective: Lung adenocarcinoma (LUAD) is one of the most common cancers in the world. Protein regulator of cytokinesis 1 (PRC1) plays a role in the tumorigenesis and development of several cancers, including LUAD. The aim of the present study is to assess the characteristics of PRC1 in LUAD in order to find a potential drug that targets PRC1.

Materials and methods: We investigated the prognostic value of PRC1 in patients with LUAD using Cox analysis of the RNA sequencing data from The Cancer Genome Atlas (TCGA) portal. A link between PRC1 and LUAD progression, cigarette smoking mutation count, aneuploidy, and hypoxia scores was assessed. The relationship between PRC1 and tumor-infiltrating immune cells in LUAD was analyzed and Gene Set Enrichment Analysis (GSEA) was used to study the PRC1-related biological process and signal pathways. Potential drugs targeting PRC1 were identified using DrugBank database and molecular docking.

Results: PRC1 expression was significantly increased in LUAD. PRC1 could be, therefore, a prognostic biomarker for predicting overall survival in LUAD. PRC1 expression was also related to cancer stage and patient's smoking history. PRC1 positively correlated with mutation count, aneuploidy and hypoxia scores. It was also significantly related to tumor-infiltrating immune cells, especially the activated mast cells. GSEA revealed that PRC1 might be correlated with cell cycle, cytokinesis and p53 signaling pathway. Additionally, fostamatinib was found to be a potential drug targeting PRC1.

Conclusions: PRC1 may have a prognostic value for patients with LUAD, and be correlated with the mutation count, aneuploidy, hypoxia and tumor-infiltrating immune cells. Fostamatinib was found to be a potential drug targeting PRC1 in LUAD.

MeSH terms

  • Adenocarcinoma of Lung* / drug therapy
  • Adenocarcinoma of Lung* / metabolism
  • Aneuploidy
  • Cell Cycle Proteins*
  • Humans
  • Hypoxia
  • Lung Neoplasms* / drug therapy
  • Molecular Docking Simulation
  • Pyridines / pharmacology
  • Pyridines / therapeutic use

Substances

  • Cell Cycle Proteins
  • fostamatinib
  • PRC1 protein, human
  • Pyridines