Identifying a cervical cancer survival signature based on mRNA expression and genome-wide copy number variations

Exp Biol Med (Maywood). 2022 Feb;247(3):207-220. doi: 10.1177/15353702211053580. Epub 2021 Oct 21.

Abstract

Cervical cancer mortality is the second highest in gynecological cancers. This study developed a new model based on copy number variation data and mRNA data for overall survival prediction of cervical cancer. Differentially expressed genes from The Cancer Genome Atlas dataset detected by univariate Cox regression analysis were further simplified to six by least absolute shrinkage and selection operator (Lasso) and stepwise Akaike information criterion (stepAIC). The study developed a six-gene signature, which was further verified in independent dataset. Association between immune infiltration and risk score was investigated by immune score. The relation between the signature and functional pathways was examined by gene set enrichment analysis. Ninety-nine differentially expressed genes were detected, and C11orf80, FOXP3, GSN, HCCS, PGAM5, and RIBC2 were identified as key genes to construct a six-gene signature. The prognostic signature showed a significant correlation with overall survival (hazard ratio, HR = 3.45, 95% confidence interval (CI) = 2.08-5.72, p < 0.00001). Immune score showed a negative correlation with the risk score calculated by the signature (p < 0.05). Four immune-related pathways were closely associated with risk score (p < 0.0001). The six-gene prognostic signature was an effective tool to predict overall survival of cervical cancer. In conclusion, the newly identified six genes may be considered as new drug targets for cervical cancer treatment.

Keywords: Copy number variants; cervical cancer; differentially expressed genes; immune score; prognostic signature; risk score; survival analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Biomarkers, Tumor / genetics
  • Chromosomes, Human
  • DNA Copy Number Variations*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Nomograms
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / genetics*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / mortality*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • RNA, Messenger