Different Expressions and Methylation Patterns of cGAS and STING in Cervical Cancer

Ruimin Wang1,2, Shuling Liu3, Rui Wang4,5

  • 1Department of Obstetrics and Gynecology, Suqian Affiliated Hospital of Xuzhou Medical University, No. 138 Huanghe Road, Suqian City, 223806, China.

Abstract

Insights

The cGAS-STING pathway is crucial in cervical cancer. This study found increased cGAS and decreased STING expression correlate with poor prognosis and reduced T cell infiltration in cervical squamous cell carcinoma.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a key component of innate immunity influencing cancer development.
  • The roles of cGAS-STING pathway genes in cervical squamous cell carcinoma (CESC), including their expression, methylation, immune function, and prognostic significance, remain incompletely understood.

Purpose of the Study:

  • To investigate the expression patterns of cGAS and STING in cervical cancer.
  • To analyze the correlation between cGAS-STING expression, T cell infiltration, and patient prognosis in CESC.
  • To explore the potential role of DNA methylation in regulating cGAS-STING expression in CESC.

Main Methods:

  • Analysis of cGAS and STING mRNA and protein expression in TCGA cervical cancer datasets and cell lines.
  • Examination of CD4+ and CD8+ T cell infiltration in relation to STING expression levels.
  • Kaplan-Meier survival analysis based on STING protein expression.
  • Validation of cGAS and STING protein expression using immunohistochemistry (IHC) on clinical CESC samples.

Main Results:

  • Cervical tumors exhibit elevated cGAS expression and reduced STING expression compared to normal tissues, impacting both mRNA and protein levels.
  • Decreased STING expression is associated with reduced CD4+ and CD8+ T cell infiltration and poorer patient prognosis.
  • cGAS and STING mRNA levels correlate with tumor stage, grade, metastasis, and histology, suggesting their involvement in cancer progression.
  • Distinct DNA methylation patterns were observed for cGAS and STING, potentially explaining their differential expression.

Conclusions:

  • The study reveals altered expression and methylation patterns of cGAS and STING in cervical cancer.
  • These alterations are linked to immune T cell infiltration and patient prognosis, highlighting the cGAS-STING pathway's significance in CESC.
  • Further mechanistic research is warranted to fully elucidate the cGAS-STING pathway's role in cervical squamous tumors.

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