Work

Exosomal gene signature in esophageal carcinoma: Insights from single-cell and bulk RNA sequencing

Year: 2025

Type: article

Abstract: • A nine-gene exosomal signature was constructed using scRNA-seq and multi-omics data. • The risk score correlates strongly with prognosis in esophageal carcinoma patients. • Immune checkpoint gene expression is significantly associated with the risk score. • The model predicts potential response to immunotherapy in ESCA. • Genomic alterations linked to the risk score offer insights for personalized therapy. Esophageal squamous cell carcinoma (ESCA) remains a lethal disease with few reliable biomarkers for early diagnosis or treatment selection. In this study, we combined bulk RNA-seq (TCGA-ESCA, GSE53625) and single-cell RNA-seq (GSE196756) data to derive and characterize an exosome-related gene signature. Using LASSO-Cox regression on 121 literature-curated exosomal genes, we established a nine-gene risk model that stratified ESCA patients into high- and low-risk groups with significantly different overall survival. This signature was validated computationally in two independent bulk cohorts and shown to correlate with established clinical parameters. Functional assays for one model component, HAPLN3, confirmed its tumor-suppressive role: HAPLN3 overexpression inhibited ESCA cell proliferation and promoted apoptosis. To explore immunotherapy relevance, we analyzed anti–PD-L1 response in the IMvigor210 bladder cancer cohort—chosen because of shared squamous histology and PD-L1 pathways—to show that low-risk patients exhibited higher response rates and longer survival. Finally, single-cell analysis mapped each signature gene to specific tumor microenvironment compartments, and integrative genomic profiling linked risk scores to copy number variation and DNA methylation changes. Together, our findings define a functionally informed exosomal biomarker panel for ESCA prognosis and suggest its potential to guide immunotherapy, with further validation in ESCA-specific immunotherapy cohorts underway.

Source: Translational Oncology

DOI: 10.1016/j.tranon.2025.102490

Authors: Hui Li, Pei Huang, YunJiao Wang, Min Zhang, DongLing Gao

Institution: First Affiliated Hospital of Zhengzhou University

Language: English

Topic: Extracellular vesicles in disease

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,390