Serpin family H member 1 and its related collagen gene network are the potential prognostic biomarkers and anticancer targets for glioma

J Biochem Mol Toxicol. 2024 Jan;38(1):e23541. doi: 10.1002/jbt.23541. Epub 2023 Sep 15.

Abstract

Serpin family H member 1 (SERPINH1) is responsible for encoding the protein known as heat shock protein 47, which functions as a molecular chaperone specific to collagen (COL). This protein has been identified as a potential therapeutic target for COL-related disorders. In this study, we aimed to investigate the role of SERPINH1 in the tumorigenicity of gliomas. To achieve this, we utilized various bioinformatics tools to analyze gene expression, overall survival, protein-protein interactions, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and Gene Set Enrichment Analysis (GSEA). Based on The Cancer Genome Atlas database revealed that SERPINH1 and four COL family members (COL1A1, COL3A1, COL4A1, and COL4A2) expression are significantly upregulated in glioma tissues compared with normal nontumor tissues. GO, KEGG, and GSEA analyses exhibited that SERPINH1 is implicated in the establishment and degradation of COL-containing extracellular matrix (ECM), focal adhesion, and ECM-receptor interaction in glioma. SERPINH1 is an independent prognostic factor, exhibiting a positive association with the augmentation of neutrophils and macrophages, as well as the manifestation of immune checkpoint molecules within glioma. Experimental assessments conducted both in vitro and in vivo demonstrated that the suppression of SERPINH1 impeded the migratory, invasive, and proliferative capacities of glioma cells, while concurrently fostering cellular apoptosis. Consequently, SERPINH1 emerges as an oncogenic gene and an independent prognostic marker for glioma, potentially facilitating the advancement of immunotherapeutic interventions for the treatment of glioma.

Keywords: glioma; immune checkpoints; immune infiltration; immunotherapy; prognosis.

MeSH terms

  • Biomarkers
  • Extracellular Matrix
  • Gene Regulatory Networks
  • Glioma* / genetics
  • Humans
  • Prognosis
  • Serpins* / genetics

Substances

  • Biomarkers
  • Serpins
  • SERPINH1 protein, human