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Updated: Jun 14, 2025
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Development and Validation of a Comprehensive Analysis of the Competing Endogenous circRNA/miRNA/mRNA Network for the
Abstract:
Immunotherapy for esophageal squamous cell carcinoma (ESCC) exhibits notable variability in efficacy. Concurrently, recent research emphasizes circRNAs' impact on the ESCC tumor microenvironment. To further explore the relationship, we leveraged circRNA, microRNA, and mRNA sequence datasets to construct a comprehensive immune-related circRNA-microRNA-mRNA network, revealing competing endogenous RNA (ceRNA) roles in ESCC. The network comprises 16 circular RNAs, 13 microRNAs, and 1,560 mRNAs. Weighted gene co-expression analysis identified immune-related modules, notably cancer-associated fibroblast (CAF) and myeloid-derived suppressor cell modules, correlating significantly with immune and stemness scores. Among them, the CAF module plays a crucial role in extracellular matrix function and effectively discriminates ESCC patients. Four hub collagen family genes within CAF correlated robustly with CAF, macrophage infiltration, and T-cell exclusion. In-house sequencing and RT-qPCR validated their elevated expression. We also identified CAF module-targeting drugs as potential ESCC treatments. In summary, we established an immune-related circRNA-miRNA-mRNA network that not only illuminates ceRNA functionality but also highlights circRNAs' involvement in the CAF through collagen gene targeting. These findings hold promise to predict ESCC immune landscapes and therapy responses, ultimately aiding in more personalized and effective clinical decision-making.
Insights
This study reveals a network of circular RNAs, microRNAs, and mRNAs influencing esophageal squamous cell carcinoma (ESCC) immunity. Targeting cancer-associated fibroblasts via collagen genes offers potential new treatments for ESCC.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Immunotherapy efficacy for esophageal squamous cell carcinoma (ESCC) is highly variable.
- Circular RNAs (circRNAs) are increasingly recognized for their role in the ESCC tumor microenvironment.
- Understanding the complex interactions between circRNAs, microRNAs, and mRNAs is crucial for deciphering ESCC pathogenesis.
Purpose of the Study:
- To construct and analyze an immune-related circRNA-microRNA-mRNA network in ESCC.
- To investigate the competing endogenous RNA (ceRNA) network's role in the ESCC tumor microenvironment.
- To identify potential therapeutic targets and biomarkers for ESCC based on this network.
Main Methods:
- Leveraged circRNA, microRNA, and mRNA sequence datasets.
- Constructed a comprehensive immune-related circRNA-microRNA-mRNA network.
- Performed weighted gene co-expression network analysis (WGCNA) and validated gene expression via RT-qPCR.
Main Results:
- A network of 16 circRNAs, 13 microRNAs, and 1,560 mRNAs was established, demonstrating ceRNA activity.
- Cancer-associated fibroblast (CAF) and myeloid-derived suppressor cell modules were identified and correlated with immune and stemness scores.
- Four hub collagen genes within the CAF module were validated as significantly upregulated and associated with immune cell infiltration and exclusion, distinguishing ESCC patients.
Conclusions:
- The study established a novel immune-related circRNA-miRNA-mRNA network in ESCC, highlighting circRNA's role in CAF regulation via collagen genes.
- The identified CAF module and its hub genes serve as potential biomarkers for predicting ESCC immune landscapes and therapy responses.
- Targeting the CAF module, particularly collagen genes, presents a promising strategy for developing personalized and effective ESCC treatments.
