Leucine Rich Repeat LGI Family Member 3: Integrative Analyses Support Its Prognostic Association with Pancreatic Adenocarcinoma

Leucine rich repeat LGI family member 3 (LGI3) is a member of the LGI protein family. Previous studies of our group have reported that LGI3 is expressed in adipose tissue, skin and brain, and serves as a multifunctional cytokine. LGI3 may also be involved in cytokine networks in various cancers. This study aimed to analyze differentially expressed genes in pancreatic adenocarcinoma (PAC) tissues and PAC cohort data in order to evaluate the prognostic role of LGI3. The expression microarray and the PAC cohort data were analyzed by bioinformatic methods for differential expression, protein-protein interactions, functional enrichment and pathway analyses, gene co-expression network analysis, and prognostic association analysis. Results showed that LGI3 expression was significantly reduced in PAC tissues. Nineteen upregulated genes and 31 downregulated genes in PAC tissues were identified as LGI3-regulated genes. Protein-protein interaction network analysis demonstrated that 92% (46/50) of the LGI3-regulated genes that were altered in PACs belonged to a protein-protein interaction network cluster. Functional enrichment and gene co-expression network analyses demonstrated that these genes in the network cluster were associated with various processes including inflammatory and immune responses, metabolic processes, cell differentiation, and angiogenesis. PAC cohort analyses revealed that low expression levels of LGI3 were significantly associated with poor PAC prognosis. Analysis of favorable or unfavorable prognostic gene products in PAC showed that 93 LGI3-regulated genes were differentially associated with PAC prognosis. LGI3 expression was correlated with the tumor-infiltration levels of various immune cells. Taken together, these results suggested that LGI3 may be a potential prognostic marker of PAC.