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Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker
Published on: September 15, 2023
Integrative single-cell and bulk transcriptomics define cell death patterns and ZDHHC22 in gastric cancer progression
Jiaming Wu1, Cong Chen2, Guangjian Dou1
1Department of Gastrointestinal Surgery, The First Hospital of Jiaxing & The First Affiliated Hospital of Jiaxing University, No.1882 Zhonghuan South Road, Jiaxing, Zhejiang, 314051, China.
BMC Medical Genomics
|May 30, 2026
Summary
Gastric cancer shows molecular subtypes influencing outcomes. Identifying cell death patterns and biomarkers like ZDHHC22 can guide personalized treatments and predict drug resistance.
Area of Science:
- Oncology
- Bioinformatics
- Genomics
Background:
- Gastric cancer presents a significant global health challenge with high mortality.
- Current treatments offer limited long-term survival, necessitating better prognostic and predictive biomarkers.
- Understanding gastric cancer's molecular heterogeneity is crucial for therapeutic advancement.
Purpose of the Study:
- To investigate gastric cancer heterogeneity using integrated single-cell and bulk RNA sequencing data.
- To identify molecular subtypes, cell communication networks, and cell death patterns.
- To explore the relationship between stemness, posttranslational modifications, prognosis, and drug sensitivity.
Main Methods:
- Acquired single-cell RNA sequencing (scRNA-seq) data from GEO and bulk RNA-seq data from TCGA.
- Performed cell communication, pseudotime, and cell death (cuproptosis, ferroptosis, autophagy, pyroptosis) analyses on scRNA-seq data.
- Conducted stemness, survival, drug sensitivity, and posttranslational modification (PTM) analyses on TCGA data.
Main Results:
- Identified three distinct molecular subtypes of gastric cancer with unique characteristics and cell death profiles.
- Discovered subtype-specific cell-cell communication and dynamic cellular states via pseudotime analysis.
- Found "cell death 2" and high cuproptosis scores as independent predictors of poor prognosis, with specific gene expression patterns in high-risk groups.
- Observed inferred drug resistance, especially to LBH589, in samples with low stemness and high pyroptosis.
- Identified ZDHHC22 as a potential protective prognostic factor associated with cell death modulation.
Conclusions:
- Gastric cancer exhibits significant molecular heterogeneity, influencing prognosis and drug response.
- Distinct cell death patterns and PTM features are key determinants of patient outcomes.
- The identified biomarkers and drug resistance profiles offer potential for personalized gastric cancer therapy.