Abstract:  Objective To analyze the transcriptome signatures of diffuse gastric cancer (DGC) and the expression of hub gene LUM (Lumican). Methods A total of 29 gastric cancer (GC) tissue and their corresponding adjust normal tissue samples were collected from patients who underwent GC resection between January 2021 and December 2021 at Guangxi Medical University Cancer Hospital, of which 5 were used to obtain mRNA expression profiling of DGC by RNA sequencing (RNA-Seq). Differentially expressed genes (DEGs) were analyzed by GO and KEGG. The protein-protein interaction (PPI) network of DEGs was constructed by cytoscape, and then the dominant gene set was evaluated. Based on the transcriptome and clinical data of GC in TCGA database, the gene expression and the prognosis were analyzed. RT-qPCR was used to examine the expression of hub gene LUM in other 24 GC tissues. Results Compared with normal adjacent tissues, a total of 175 DEGs in DGC, of which 91 genes were up-regulated and 84 genes were down-regulated. GO and KEGG enrichment analysis revealed that there were multiple ways involved in extracellular matrix related cellular processes and malignant progression in DGC. The EMT-associated gene set was dominant in DGC. The expression levels of COL6A3, LUM, COL1A2, SPARC, COL1A1, CDH11, COL3A1, NID2, BGN and COL4A1 in the EMT-associated gene set were higher than those in the adjacent normal and intestinal GC (all P<0.05). DGC patients with high expression of the hub gene LUM had a shorter overall survival (P=0.043). The RT-qPCR results showed that LUM was highly expressed in GC, and the expression level in DGC was higher than that in the intestinal and mixed GC(all P<0.05). Conclusions The transcriptome characteristics of DGC shows that EMT-associated gene set is in a dominant position. The expression of hub gene LUM is increased in DGC and the overall survival of patients with high LUM expression is shortened. LUM can be used as a potential prognostic marker and therapeutic target for DGC.

Key words: Gastric cancer, Diffuse gastric cancer, RNA sequencing, EMT, LUM