Abstract
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.
Highlights
Gastric cancer (GC) is one of the common malignant tumors threatening human health, causing ∼1,033,701 new cases and 782,685 deaths worldwide in 2018 [1]
We found that the mRNA levels of LGMN were higher in diffuse-type GC compared with intestinaltype GC (P < 0.05, Figure 1C)
We found that the LGMN expression was much higher (P < 0.05) in GC patients with stage III/IV compared to GC patients with tumor stage I/II (Figure 5A)
Summary
Gastric cancer (GC) is one of the common malignant tumors threatening human health, causing ∼1,033,701 new cases and 782,685 deaths worldwide in 2018 [1]. Peritoneal metastasis is more commonly observed in diffuse-type GC than other types [4,5,6], which may contribute to their worse survival. Considerable advances have been made in the management of GC, such as chemotherapy, targeted therapy, and immunotherapy, the 5-year overall survival (OS) of GC patients with peritoneal metastasis remains dismal [7, 8]. The molecular biomarkers and mechanisms underlying peritoneal metastasis have not been well-established in GC patients. It is essential to identify novel molecular biomarkers for early diagnosis, prevention, and targeted therapy for GC patients. The association between LGMN and gastric cancer (GC) has not yet been fully elucidated. We performed a comprehensive analysis of the role of LGMN in clinicopathologic characteristics and survival of GC patients
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