Construction of an immune-related gene signature for prediction of prognosis in patients with cervical cancer

Int Immunopharmacol. 2020 Nov:88:106882. doi: 10.1016/j.intimp.2020.106882. Epub 2020 Aug 13.

Abstract

Cervical cancer (CeCa) is becoming an intractable public health issue worldwide. Emerging evidence uncovers that the tumor progression and prognosis of patients with CeCa are tightly associated with the abundance of tumor-infiltrating immune cells. In the current study, the abundance of tumor-infiltrating immune cells in CeCa samples was assessed by using the ssGSEA, thereby generating two immune-related groups according to the immune status. A 4-gene prognostic signature (RIPOR2, DAAM2, SORBS1, and CXCL8) was next established based on the grouping and its predictive capability was validated by multiple analyses. The TIMER database was used to evaluate the association between 4 hub gene expression and immune cell infiltration. Immunophenoscore (IPS) was used to assess response to immune checkpoint inhibitors in CeCa samples. As the results, a novel grouping strategy based on immune cell infiltration was developed and validated. Based on the grouping, a 4-gene signature was identified to be an independent prognostic indicator for overall survival (OS) in CeCa patients. Among the 4 hub genes, RIPOR2 and CXCL8 expression were significantly correlated with immune cell infiltration. Besides, higher immune checkpoints expression and IPS scores were found in the 4-gene signature low-risk group, suggesting a more immunoactive status that tended to respond to immune checkpoint inhibitors. To sum up, a novel immune-related signature is established to predict CeCa patients' prognosis and also associated with response to immune checkpoint inhibitors, which might be a promising prognostic stratification strategy and innovate therapeutic management.

Keywords: Cervical cancer; Immune checkpoint inhibitor response; Immune signature; Prognosis; Risk score.

MeSH terms

  • Biomarkers, Tumor / immunology*
  • Computational Biology / methods
  • Correlation of Data
  • Databases, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic / immunology
  • Genes / immunology*
  • Humans
  • Immune Checkpoint Inhibitors / immunology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immune Checkpoint Proteins / genetics
  • Immune Checkpoint Proteins / metabolism
  • Immunophenotyping
  • Immunotherapy
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Nomograms
  • Prognosis
  • Regression Analysis
  • Risk Factors
  • Transcriptome / immunology
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / immunology*

Substances

  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • Immune Checkpoint Proteins