Identification of Genes Universally Differentially Expressed in Gastric Cancer

Owing to the remarkable heterogeneity of gastric cancer (GC), population-level differentially expressed genes (DEGs) identified using case-control comparison cannot indicate the dysregulated frequency of each DEG in GC. In this work, first, the individual-level DEGs were identified for 1,090 GC tissues without paired normal tissues using the RankComp method. Second, we directly compared the gene expression in a cancer tissue to that in paired normal tissue to identify individual-level DEGs among 448 paired cancer-normal gastric tissues. We found 25 DEGs to be dysregulated in more than 90% of 1,090 GC tissues and also in more than 90% of 448 GC tissues with paired normal tissues. The 25 genes were defined as universal DEGs for GC. Then, we measured 24 paired cancer-normal gastric tissues by RNA-seq to validate them further. Among the universal DEGs, 4 upregulated genes (BGN, E2F3, PLAU, and SPP1) and 1 downregulated gene (UBL3) were found to be cancer genes already documented in the COSMIC or F-Census databases. By analyzing protein-protein interaction networks, we found 12 universally upregulated genes, and we found that their 284 direct neighbor genes were significantly enriched with cancer genes and key biological pathways related to cancer, such as the MAPK signaling pathway, cell cycle, and focal adhesion. The 13 universally downregulated genes and 16 direct neighbor genes were also significantly enriched with cancer genes and pathways related to gastric acid secretion. These universal DEGs may be of special importance to GC diagnosis and treatment targets, and they may make it easier to study the molecular mechanisms underlying GC.