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

## TL;DR

This study explores how cGAS and STING genes behave in cervical cancer, finding that their expression and methylation patterns affect immune cell infiltration and patient outcomes.

## Contribution

The study reveals novel expression and methylation patterns of cGAS and STING in cervical cancer linked to immune infiltration and prognosis.

## Key findings

- cGAS is upregulated while STING is downregulated in cervical tumors, correlating with reduced T cell infiltration and poor prognosis.
- cGAS and STING mRNA levels change with tumor stage, grade, and metastasis, confirmed by immunohistochemistry in clinical samples.
- Differential DNA methylation patterns of cGAS and STING may explain their altered expression in cervical cancer.

## Abstract

The cGAS–STING pathway has established itself as a critical innate immune pathway that has the ability to significantly affect tumor initiation and progression. The expression, methylation, immunological functions, and prognostic importance of cGAS–STING pathway‐related genes in cervical squamous cancer (CESC) patients have not yet been thoroughly elucidated.

First, we explored the expression of cGAS and STING in cervical carcinoma samples from TCGA by comparing the mRNA and protein levels of cGAS and STING in both TCGA cervical tumor patient samples and cervical tumor cell lines. Second, we examined the CD4+T and CD8+T cell infiltration in STING high and low samples and made Kaplan–Meier prognosis analysis of STING protein expression. Third, to verify the findings in TCGA public datasets, we retrospectively selected 40 cervical squamous carcinoma patients and 10 normal cervical tissues and evaluated cGAS and STING protein expression using immunohistochemistry (IHC). All patients have detailed clinical information, which includes age, FIGO stage, menstruation status, follow‐up time, histology, tumor diameter, and serum tumor markers.

In both cervical tumor patient samples and cell lines, we observed that cGAS is increased, whereas STING is decreased in tumors, which leads to decreased CD4+T and CD8+T cell infiltration and poor prognosis. Furthermore, the cGAS mRNA transcript showed a gradual increase and STING mRNA showed a decrease according to the tumor stage, tumor grade, metastasis status, and histology types. We confirmed the expression of cGAS and STING proteins in clinical cervical tumor samples using IHC. Mechanically, cGAS and STING showed different DNA methylation patterns, which might contribute to the differences in cGAS and STING mRNA and protein levels.

Our work identified different expressions and methylation patterns of cGAS and STING in cervical cancer and their correlation with immune T cell infiltration and prognosis. More mechanistic study is needed to understand the cGAS–STING pathway in cervical squamous tumor.