CLSPN is a potential biomarker associated with poor prognosis in low-grade gliomas based on a multi-database analysis

Curr Res Transl Med. 2022 Sep;70(4):103345. doi: 10.1016/j.retram.2022.103345. Epub 2022 Apr 26.

Abstract

Background: The oncogene CLSPN, also known as claspin, has regulatory effects in a variety of tumours; however, it is not clear whether CLSPN is a therapeutic target in low-grade gliomas (LGG). In this study, the prognostic value of CLSPN in LGG and its role as an immunotherapeutic target were evaluated.

Methods: Transcriptome and methylation data for thousands of patients with glioma were collected from various databases, including The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and Gene Expression Omnibus. Subsequently, a series of bioinformatics methods were used to evaluate the relationships between CLSPN and prognosis, clinical features, methylation status, immune cells, and molecular signaling pathways in LGG.

Results: CLSPN expression levels were positively correlated with major malignant characteristics of LGG, and low expression of CLSPN was associated with a better prognosis. The methylation sites cg04263115 and cg06100291 negatively regulated the expression of CLSPN, and increased methylation levels at these sites were related to a longer survival time in patients with LGG. CLSPN was positively correlated with tumour-infiltrating immune cells and showed high copy number variation in these cells. There was a positive regulatory relationship between CLSPN expression and programmed death-1 (PD-1) and programmed cell death ligand 1 (PD-L1). A gene set enrichment analysis revealed that CLSPN activates a variety of cancer signaling pathways.

Conclusion: CLSPN was identified as an independent risk factor for LGG with excellent prognostic value.

Keywords: CLSPN; Immunotherapy; LGG; PD-L1; Prognosis.

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms* / diagnosis
  • Brain Neoplasms* / genetics
  • DNA Copy Number Variations
  • Glioma* / diagnosis
  • Glioma* / genetics
  • Humans
  • Neoplasm Grading
  • Prognosis

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • CLSPN protein, human