LAMC1 is a Novel Prognostic Factor and a Potential Therapeutic Target in Gastric Cancer

Abstract

To investigate the role of LAMC1 in gastric cancer (GC), if it is of great importance to identify tumour driver genes with prognostic value. Patients and Methods: GC-related gene expression profile data were downloaded from TCGA. R-limma package and univariate Cox regression were used to identify the differentially expressed genes (DEGs) and survival-genes, respectively. Then, the ClusterProfiler package was used to analyse the Gene Ontology and pathway enrichment of DEGs. Cytoscape was used to build a protein interaction network (PPI) and identify key genes. The GEPIA2 and TIMER databases were used to validate the differential expression of LAMC1. The relationship between LAMC1 and the prognosis of GC was analysed by the KM. GSEA and GSVA were used to analyse the major activated and mutated pathways, respectively. Real-time fluorescence quantitative PCR (RT-qPCR) was used to reidentify the expression of LAMC1 in GES-1 and 5 GC cell lines. Finally, we explored the relationship between LAMC1 and FGFR1. Results: A total of 266 DEGs were be selected, which were mainly enriched in extracellular structure organization. LAMC1 was identified as one of the hub genes. The expression of LAMC1 was significantly higher in GC tissue than in paracancerous tissues, and the prognosis of the GC patient with high expression of LAMC1 was relatively poor. Univariate and multivariate Cox analysis indicated that LAMC1 could be used as an independent prognostic indicator. The results of GSEA and GSVA showed that LAMC1 was mainly enriched in pathways such as MYOGENESIS and UV_RESPONSE_DN. The RT-qPCR results showed that the expression level in AGS cells was significantly higher than that in gastric epithelial cells. LAMC1 may play a role in the development of gastric cancer by influencing FGFR1. Conclusion: LAMC1 may mediate the occurrence and development of GC and has potential as a biomarker for the prognosis and treatment of GC.

The role and significance of SVIL protein in the occurrence and development of gastric cancer

“…Laminin is an important component of extracellular matrix, with different tissue distributions and functions concerning different tissue subtypes. Amogn them, LAMB1 and LAMC1 were respectively confirmed to be highly expressed in colorectal cancer and endometrial cancer, both of which were recognized to be prognostic factors and potential therapeutic targets [10,11]. Growth arrest specific gene protein 6 (GAX6) is a ligand of Tyro3/Axl/Mer receptor tyrosine kinase in the receptor tyrosine kinase subfamily.…”