Comprehensive molecular characterization of high-stemness gastric cancer cells using single-cell transcriptomics,
Ziyi Wang1,2,3, Xuehao Li3, Jin Wang4
1Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China.
NPJ Precision Oncology
|December 17, 2025
Summary
This study identifies key genes in high-stemness gastric cancer (GC) cells, revealing their role in tumor aggressiveness and chemoresistance. These findings offer potential biomarkers for personalized GC treatment strategies.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Gastric cancer (GC) presents significant clinical challenges due to late diagnosis, heterogeneity, and poor prognosis.
- Tumor stemness is a critical driver of GC aggressiveness and therapeutic resistance.
- Systematic characterization of high-stemness GC cells and their molecular features is limited.
Purpose of the Study:
- To identify and characterize high-stemness GC cells using integrated multi-omics data.
- To explore genomic instability, genetic susceptibility, and microenvironmental interactions in high-stemness GC cells.
- To develop a predictive model for high-stemness GC cells and validate potential therapeutic targets.
Main Methods:
- Integrated analysis of single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and bulk RNA-seq data.
- Calculation of stemness scores using CytoTRACE and classification of cell subpopulations.
- Genomic and cell-cell communication profiling, WGCNA, machine learning for feature screening, and SHAP analysis for model interpretation.
- Experimental validation via gene knockdown and assessment of pathway activity and chemosensitivity.
Main Results:
- High-stemness GC cells exhibit enhanced intercellular signaling, metabolic reprogramming, and stemness pathway activity.
- Five robust HighStem features identified: APMAP, MAPRE1, GLB1, TSPAN6, and CDKN2A.
- A Support Vector Machine (SVM) model using these genes achieved high accuracy (AUC=0.973) in distinguishing HighStem cells.
- Gene knockdown reduced JAK1-STAT3 pathway activity and increased GC cell sensitivity to chemotherapy (5-FU, cisplatin).
Conclusions:
- This study provides a comprehensive molecular and functional characterization of high-stemness GC cells.
- Identified signature genes and predictive models offer insights into GC stemness biology and personalized therapeutic strategies.
- The core genes may serve as potential biomarkers for predicting treatment outcomes and monitoring therapeutic resistance in GC.
