Introduction
Gastric cancer (GC) is the fifth most common malignancy worldwide and the fifth leading cause of cancer-related mortality. Despite advances in diagnosis and treatment options, the molecular mechanisms behind the pathogenesis of GC are not fully understood. Whole transcriptome analysis enables comprehensive characterization of gene expression changes associated with malignant transformation that may contribute to the identification of novel diagnostic and therapeutic targets.
Aims & Methods
The objective of this study was to conduct transcriptome analysis of GC tissue and adjacent non-neoplastic mucosa to identify key molecular signatures involved in gastric carcinogenesis. The study cohort comprised 48 patients with paired gastric cancer and adjacent non-neoplastic mucosa samples. The mean age was (67.5 ± 10.8 years) and the majority were male (75.0%). Whole-transcriptome RNA sequencing was performed using the Illumina NovaSeq X Plus platform. Reads were quality controlled, aligned to the human reference genome (GRCh37) using STAR, and quantified with Salmon using the nf-core/rnaseq pipeline. Differential gene expression analysis between paired groups was performed with DESeq2 (FDR <0.05, |log2FC| >1). Subgroup analyses according to tumor invasion stage (T1–T2 vs T3–T4) and pathway enrichment analyses were additionally performed.
Results
Whole transcriptome analysis demonstrated clear separation between gastric cancer and matched adjacent non-neoplastic mucosa samples on principal component analysis, indicating distinct gene expression profiles. Differential expression analysis identified numerous significantly dysregulated genes in gastric cancer tissue. Among the most upregulated genes were KRT16, CHI3L1, CLDN1, INHBA and CEMIP, mainly associated with epithelial remodeling, invasion, and tumor progression. In contrast, ATP4A, ATP4B, PGA3, PGA4 and LIPF were among the most downregulated genes, reflecting loss of normal gastric secretory and metabolic functions. These findings indicate profound molecular reprogramming during gastric carcinogenesis. Additional analysis comparing the tumor invasion stage (T1-2 versus T3-4) identified 11 altered genes with the most significant overexpression of KRT4, S100A7, A2ML1 and KRT23 in tumors with deeper invasion. These findings indicate profound molecular reprogramming during gastric carcinogenesis and progression.
Conclusion
Gastric cancer tissue demonstrates distinct transcriptomic alterations involved in extracellular matrix remodeling and tumor progression. Genes linked to epithelial differentiation and cytoskeletal organization were enriched in tumors with deeper invasion, suggesting their role in disease progression. Whole transcriptome analysis may provide valuable insights into gastric carcinogenesis and identify potential molecular biomarkers and therapeutic targets.