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Updated: Jul 2, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Single-cell and pseudobulk analyses reveal hidden mitochondrial expression imbalance in gastric cancer
Le Chang1, Jingwen Hou1, Yingying Li1
1Henan Key Laboratory for Helicobacter pylori and Digestive Tract Microecology, The Fifth Affiliated Hospital of Zhengzhou University; Institute of Rehabilitation Medicine, Henan Academy of Innovations in Medical Science; Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Background:
Mitochondrial function is essential for biology, particularly in cancer. However, cell-type-specific expression patterns of conserved mitochondrial genes in gastric cancer (GC) remain unclear. We herein raised and tested a novel hypothesis of "mitochondrial conserved gene expression homeostasis imbalance" in GC cohorts with single-cell resolution.
Methods:
This work analyzed an open-accessed scRNA-seq dataset (GSE206785, 24 GC patients, 48 samples) with Seurat and defined 43 clusters grouped into 15 cell subtypes. In parallel, Pseudobulk profiles were generated to simulate bulk RNA-seq. A mitochondrial conserved gene score was computed by Seurat AddModuleScore, GSVA, and AUCell. Mitochondria-related biomarkers were also screened, validated, and incorporated into a mitochondria-dependent prognostic model that was further evaluated.
Results:
Without considering cell-type-specific expression patterns, Pseudobulk analysis showed no significant differences in mitochondrial conserved gene expression between GC and control samples. In contracst, single-cell analysis found a cell-type-specific imbalance, under which tumor-associated epithelial cells displayed relatively elevated mitochondrial conserved gene expression, while non-epithelial cells showed reduced. Notably, survival analyses identified gene KRT7 and KLRC1 as robust prognostic biomarkers for early GC.
Conclusion:
Our findings support a mitochondrial conserved gene expression homeostasis imbalance in GC, which is characterized by compartment-specific mtGene expression imbalance. Also, KRT7 and KLRC1 emerge as prognostic markers for therapies aimed at restoring mitochondrial homeostasis in GC.
