miR-378a-5p exerts tumor-suppressive effects on esophageal squamous cell carcinoma after neoadjuvant immunotherapy by downregulating APOC1/CEP55

Abstract

AbstractGenetic 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.