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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
miR-378a-5p exerts tumor-suppressive effects on esophageal squamous cell carcinoma after neoadjuvant immunotherapy by
Yang Pengjie1,2, Jia Rong1, Ning Pengfei3
1Inner Mongolia Medical University, Jinshan Development Zone, Hohhot, 010110, Inner Mongolia Autonomous Region, China.
Abstract:
Genetic assessment of tumors following neoadjuvant immunotherapy helps identifying targets that mediate anti-tumor immunity. In this study, we explored dysregulated RNAs in esophageal squamous cell carcinoma samples after neoadjuvant immunotherapy using deep sequencing and high-throughput screening. We identified 584 differentially expressed messenger RNAs (mRNAs), 67 differentially expressed microRNAs (miRNAs), and 1,047 differentially expressed long non-coding RNAs (lncRNAs) using differential expression analysis. Competing endogenous RNAs closely related to esophageal squamous cell carcinoma were selected via a combined Pearson's correlation test and weighted correlation network analysis. After validation using survival analysis and dry-lab and wet-lab-based studies, we identified the I-miR-378-5p-APOC1/CEP55 as a critical pathway for esophageal squamous cell carcinoma progression after neoadjuvant immunotherapy. Tumor immune infiltration analysis showed that APOC1 and CEP55 expression is associated with immune regulatory pathways and the function of multiple infiltrating immune cells. We investigated the mechanism of esophageal squamous carcinoma progression after neoadjuvant immunotherapy from the perspective of the mRNA-miRNA-lncRNA network. Furthermore, we identified accurate novel therapeutic targets and prognostic biomarkers, introduced novel perspectives to immunotherapy studies, and laid the foundation for the clinical treatment of patients with esophageal squamous carcinoma.
Insights
This study identifies a critical RNA pathway (I-miR-378-5p-APOC1/CEP55) driving esophageal squamous cell carcinoma progression post-immunotherapy. Findings reveal novel therapeutic targets and biomarkers for improved patient treatment.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Neoadjuvant immunotherapy enhances anti-tumor immunity by targeting tumor genetic alterations.
- Understanding RNA dysregulation post-immunotherapy is crucial for optimizing treatment strategies in esophageal squamous cell carcinoma (ESCC).
Purpose of the Study:
- To identify dysregulated RNAs (mRNAs, miRNAs, lncRNAs) in ESCC after neoadjuvant immunotherapy.
- To elucidate the mRNA-miRNA-lncRNA network's role in ESCC progression.
- To discover novel therapeutic targets and prognostic biomarkers for ESCC.
Main Methods:
- Deep sequencing and high-throughput screening of ESCC samples.
- Differential expression analysis to identify dysregulated RNAs.
- Pearson's correlation and weighted gene co-expression network analysis to identify competing endogenous RNAs (ceRNAs).
- Survival analysis, dry-lab, and wet-lab validation studies.
- Tumor immune infiltration analysis.
Main Results:
- Identified 584 differentially expressed mRNAs, 67 miRNAs, and 1,047 lncRNAs.
- Selected the I-miR-378-5p-APOC1/CEP55 pathway as critical for ESCC progression post-neoadjuvant immunotherapy.
- APOC1 and CEP55 expression correlated with immune regulatory pathways and immune cell function.
- Established an mRNA-miRNA-lncRNA network mechanism for ESCC progression.
Conclusions:
- The I-miR-378-5p-APOC1/CEP55 pathway is a key driver of ESCC progression after neoadjuvant immunotherapy.
- APOC1 and CEP55 are potential prognostic biomarkers and therapeutic targets.
- This research offers new insights into immunotherapy and provides a foundation for clinical ESCC treatment.
