High Level of Legumain Was Correlated With Worse Prognosis and Peritoneal Metastasis in Gastric Cancer Patients

Background: Accumulating evidence has demonstrated that legumain (LGMN) is abnormally expressed in several malignancies and functions as an oncogene. However, the association between LGMN and gastric cancer (GC) has not yet been fully elucidated. In this study, we performed a comprehensive analysis of the role of LGMN in clinicopathologic characteristics and survival of GC patients. Methods: The study had two patient cohorts, The Cancer Genome Atlas (TCGA) cohort and the Zhongshan Hospital cohort, both of which were used to analyze the role of LGMN in GC samples. The relationship between LGMN and clinicopathologic characteristics was determined by the Chi-square test and logistic regression analysis. The Kaplan-Meier method and Cox proportional hazards regression analysis were conducted to investigate the prognostic role of LGMN in GC patients. Moreover, a nomogram was constructed based on the factors that were independently associated with peritoneal metastasis. Finally, the gene set enrichment analysis (GSEA) was conducted to explore the underlying pathways through which LGMN was involved in GC progression. Results: The mRNA and protein levels of LGMN were significantly upregulated in GC tissues, especially for diffuse-type GC. High level of LGMN was independently associated with poor prognosis in both TCGA and Zhongshan cohorts. Further analysis showed that increased protein level of LGMN was related to peritoneal metastasis in GC patients. In a nomogram model, the LGMN expression could help predict the possibility of peritoneal metastasis in GC patients. LGMN was a strong determinant for prediction of peritoneal metastasis. GC patients with high LGMN expression tended to have worse survival together with more frequent diffuse-type tumors and increased risk of peritoneal metastasis. The GSEA results showed that focal adhesion, ecm receptor interaction, cell adhesion molecules cams, TGF-β signaling pathway, JAK-STAT signaling pathway, gap junction, etc. were differentially enriched in the phenotype with high LGMN expression. Conclusion: LGMN was an independent prognostic factor for OS in GC patients. Increased expression of LGMN was significantly associated with peritoneal metastasis. The nomogram based on LGMN might guide the clinical decisions for patients with GC.