Abstract
Renal cell carcinoma (RCC) typically shows resistance to immunotherapy and is associated with poor prognosis. Recent studies have revealed a role for DNA methylation in immune infiltration in different cancers, but its pattern in RCC is not well understood. In this study, we analyzed the relationships among STING promoter methylation, mRNA expression, overall survival, and immune cell infiltration in a TCGA cohort and validated the findings in an independent cohort. Additionally, we assessed these correlations in an RCC cohort from Sun Yat-sen University Cancer Center (SYSUCC) using immunohistochemistry and pyrosequencing. Our findings revealed significant hypomethylation of the STING promoter in RCC tumor tissues compared with normal tissues, which strongly correlated with increased STING mRNA expression across all three RCC cohorts. Additionally, hypomethylation of the STING promoter hypomethylation was associated with advanced clinicopathological features and poor overall survival. Moreover, we found a significant relationship between STING promoter methylation and both immune cell infiltration and the expression of immune checkpoint molecules. Our findings in the SYSUCC cohort confirmed that STING promoter methylation was related to CD4 and CD8 T-cell infiltration in RCC tumor tissues. These results suggest that methylation of the STING promoter plays a pivotal role in regulating its expression and influencing the tumor microenvironment. STING promoter methylation and expression are linked to clinicopathological characteristics, overall survival, and immune cell infiltration in RCC. We propose that further validation of STING promoter methylation represents a biomarker for predicting responses to immune checkpoint inhibitors in RCC.
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Data availability
TCGA cohort: The datasets analyzed during the current study are available in The Cancer Genome Atlas (TCGA) repository (http://cancergenome.nih.gov/). Gene expression, DNA methylation (Infinium HumanMethylation450 BeadChip), and related clinical data for clear‑cell renal cell carcinoma (ccRCC) were obtained from TCGA and processed using the ChAMP R package. The clinicopathological characteristics of the patients are summarized in Table S1. An overview of the study workflow is presented in Figure S1. CPTAC cohort and GEO datasets: The datasets generated and analyzed during the current study are available in the following repositories: gene expression and methylation data of 100 RCC samples from the CPTAC repository (https://proteomics.cancer.gov/data-portal); methylation datasets GSE70303 and GSE105260 are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo/) under accession numbers GSE70303 and GSE105260, respectively. The processed data used in this study are provided in Supplementary Tables S2, S3, S4, and S5. SYSUCC cohort: For validation of cg16983159 methylation in RCC, a total of 98 samples including 14 adjacent normal tissues and 84 tumor tissues were collected from Sun Yat-sen University Cancer Center (SYSUCC). The patients underwent surgery from 2009 to 2015 at SYSUCC, and clinical follow-up information was collected for analysis. The basic information of all the datasets included in our study is provided in Table S6.
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Acknowledgements
We thank all members of Liu’s laboratory for their advice and assistance.
Funding
This study was supported by the funds from the National Natural Science Foundation of China (grant number: 82303526 and 82403073), the Natural Science Foundation of the Hunan Province of China (grant number: 2024JJ6590, 2023JJ40842 and 2022JJ40704), the Education and Teaching Reform Research Project of Central South University (grant number: 2022JY197), the China Postdoctoral Science Foundation (grant number: 2023M743946 and 2023M733955), the Open Funds of State Key Laboratory of Oncology in South China (grant number: HN2024-04 and NH2024-07) and the Scientific Research Launch Project for new employees of the Second Xiangya Hospital of Central South University (grant number: QH20230256 and QH20230268).
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X.L., Q.L., and S.D. conceived and designed the project. S.D., Q.L., M.D., A.H., Y.G., K.Y., and Q.M. analyzed and interpreted the data. S.D., M.L., C.L., and F.M. wrote the main manuscript text. S.D. and Q.L. prepared figures. All authors contributed to the article and approved the submitted version.
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Public data was obtained from the TCGA and CPTAC were used. Clinical specimens were obtained from the Tumor Bio-bank of Sun Yat-sen University Cancer Center. The study protocol for the SYSUCC cohort was approved by the Institutional Research Ethics Committee of Sun Yat-sen University Cancer Center (B2020-310-01). All methods were conducted in accordance with relevant guidelines and regulations.
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Ding, S., Ding, M., Hu, A. et al. Prognostic significance and immune correlation of STING expression and promoter methylation in renal cell carcinoma. Sci Rep (2026). https://doi.org/10.1038/s41598-026-47187-1
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DOI: https://doi.org/10.1038/s41598-026-47187-1
