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Abstract
Background Effective biomarkers of gastric cancer (GC) are critical for early detection and improvement of early prognosis. We conducted a systematic transcriptomic study targeting the progression of different gastric lesions and the gastric carcinogenesis process and a multi-omics integration study to identify and validate novel GC biomarkers depending on a high-risk population.
Methods We portrayed the transcriptomic landscape and explored transcriptomic signatures associated with the progression of gastric lesions and the risk of early GC relying on the Early Diagnosis and Treatment of Gastric Cancer at High Prevalence Sites in Linqu County, Shandong Province. Tissue RNA sequencing was conducted for a total of 103 subjects with superficial gastritis (SG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), or gastric cancer. Statistical analysis was performed using the ‘Deseq2’ package by R4.3.3 to screen for differential genes with fold changes >1.5 and false discovery rate <0.05. Two-stage validation was conducted with a prospective follow-up of 42 subjects for the progression of gastric lesions.
Results Unsupervised clustering of transcriptomic data revealed distinct profiles from gastric lesions to GC. Six RNA clusters that possessed similar trajectories were extracted with dynamic changes in RNA profiles through mild gastric lesions (SG/CAG) and advanced gastric lesions (IM/LGIN) to GC (IDDF2024-ABS-0307 Figure 1. Transcriptomic Landscape of precancerous gastric lesions and GC (C)). We then identified 952 differentially expressed genes in subjects with GC vs. mild and advanced gastric lesions (IDDF2024-ABS-0307 Figure 2. Key genes associated with gastric lesions progression and early GC (A)). Baseline gene expression levels of GAS2L1, GGT2, SNCG, and NKX6-1 were further associated with the risk of gastric lesion progression (IDDF2024-ABS-0307 Figure 2. Key genes associated with gastric lesions progression and early GC).
Transcriptomic Landscape of precancerous gastric lesions and GC.
Key genes associated with gastric lesions progression and early GC.
Conclusions Transcriptomic analysis identified relevant key differential genes for the progression of gastric lesions and the risk of early GC, which may have translational significance for identifying particularly high-risk populations. We will further integrate the demographic data and environmental exposure information of the study subjects to construct early gastric cancer risk prediction models to promote GC prevention.