High expression of serine protease 2 (PRSS2) associated with invasion, metastasis, and proliferation in gastric cancer

Abstract

Background: Accumulating evidence indicates that the occurrence and development of tumors are related to the activation of oncogenes and the inactivation of tumor suppressor genes caused by epigenetic mechanisms. However, the function of serine protease 2 (PRSS2) in gastric cancer (GC) is still unknown. Our study aimed to find a regulation network involved in GC.

Methods: The mRNA data (GSE158662 and GSE194261) of GC and normal tissues were downloaded from the Gene Expression Omnibus (GEO) dataset. Differential expression analysis was performed using R software, and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted by using Xiantao software. Besides, we used Quantitative Real-time PCR (qPCR) to verify our conclusions. After gene knockdown, cell migration and CCK-8 experiment were carried out to detect the effect of gene on cell proliferation and invasion.

Results: Totally, 412 differentially expressed genes (DEGs) were identified from GSE158662 and 94 DEGs were identified from GSE196261. Km-plot database results indicated that PRSS2 exhibited high diagnosis worth for GC. Gene functional annotation enrichment analysis revealed that these hub mRNAs were mainly taken part in the process of tumorigenesis and development. Besides, vitro experiments showed that down-regulation of PRSS2 gene reduced the proliferation and invasion ability of GC cells.

Conclusions: Our results indicated that PRSS2 may play vital roles in the carcinogenesis and progression of GC and can be potential biomarkers for patients with GC.

Keywords: CCK-8; GEO; PRSS2; gastric cancer; qPCR.

Figure 1

Heat map and volcano map of differentially expressed genes of GSE158662 and GSE194261. (A, B) Heat map and volcano map of DEGs in GSE158662. (C, D) Heat map and volcano map of DEGs in GSE194261.

Figure 2

Gene ontology and KEGG enrichment.

Figure 3

Venn diagram of GSE158662 and GSE194261.

Figure 4

The relationship between the expression level of selected genes and overall survival of gastric cancer patients. (A–I) Relationship between various molecules including PRSS2, SIX2, FGF13 and survival of gastric cancer patients.

Figure 5

The relationship between PRSS2 and immune infiltration. (A) Immunocyte infiltration and enrichment analysis. (B, C) High expression of PRSS2 in gastric cancer is associated with less T cell infiltration.

Figure 6

Effects of PRSS2 knockdown on GC cell viability and migratory capacity in vitro. (A, B) PRSS2 expression in MGC-803 and BGC-823 cells transfected with negative control siRNA (si-NC) or siRNAs targeting PRSS2 (si-PRSS2 #1 and #2) for 48h n=3 for each group. (C, D) Cell viability was assessed using a CCK-8 assay in MGC-803 and BGC-823 cells transfected with si-NC or si-PRSS2 #1 and #2 for 48h n=6 for each group. (E, F) Transwell invasion assay was performed to determine the invasion ability of si-PRSS2-transfected MGC-803 and BGC-823 cells for 48h n=3 for each group. (G–I) qPCR detection of invasive pseudopod-related proteins Krp1, WASP-B, and Lasp1. n = 3. ^*P < 0:05, ^**P < 0:01, and ^***P < 0:001 indicate significant difference.