LAMB1 Is Related to the T Stage and Indicates Poor Prognosis in Gastric Cancer

Abstract

Background and objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Laminin is an indispensable component of basement membrane and extracellular matrix, which is responsible for bridging the internal and external environment of cells and transmitting signals. This study mainly explored the association of the LAMB1 expression with clinicopathological characteristics and prognosis in gastric cancer.

Methods: The expression data and clinical information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG). And we analyzed the relationship between LAMB1 expression and clinical characteristics through R. CIBERSORTx was used to calculate the absolute score of immune cells in gastric tumor tissues. Then COX proportional hazard models and Kaplan-Meier curves were performed to evaluate the role of LAMB1 and its influence on prognosis in gastric cancer patients. Finally, GO and KEGG analysis were applied for LAMB1-related genes in gastric cancer, and PPI network was constructed in Cytoscape software.

Results: In the TCGA cohort, patients with gastric cancer frequently generated LAMB1 gene copy number variation, but had little effect on mRNA expression. Both in the TCGA and ACRG cohorts, the mRNA expression of LAMB1 in gastric cancer tissues was higher than it in normal tissues. All patients were divided into high expression group and low expression group according to the median expression level of LAMB1. The elevated expression group obviously had more advanced cases and higher infiltration levels of M2 macrophages. COX proportional hazard models and Kaplan-Meier curves revealed that patients with enhanced expression of LAMB1 have a worse prognosis. GO/KEGG analysis showed that LAMB1-related genes were enriched in PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, etc.

Conclusions: The high expression of LAMB1 in gastric cancer is related to the poor prognosis of patients, and it may be related to microenvironmental changes in tumors.

Keywords: CIBERSORTx; GC; LAMB1; TICs; TME; gastric cancer; prognosis; survival; the β1 subunit of laminin; therapeutic target; tumor microenvironment; tumor-infiltrating immune cells.

Figure 1.

The expression of LAMB1 in gastric cancer. A-B. Comparison of LAMB1 mRNA expression between tumor and normal samples in ACRG (A) and TCGA-STAD (B). C. The relationship between mRNA of LAMB1 and copy number variation of LAMB1 in TCGA-STAD.

Figure 2.

The mRNA expression of LAMB1 in different TNM stage of gastric cancer. A-F. The association between LAMB1 mRNA expression and different T stages (A&D), different N stages (B&E), different distant metastasis status (C&F).

Figure 3.

The mRNA expression of LAMB1 in different subtype of gastric cancer. A-F. Comparison of LAMB1 mRNA expression between gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma (A&D), different histological subtype (B&E), and different molecular subtypes in TCGA-STAD (C) and ACRG (F).

Figure 4.

Differences in overall survival between LAMB1 low expression group and LAMB1 high expression group in TCGA (A) and ACRG (B).

Figure 5.

The distribution of infiltrating immune cells in the low- and high-LAMB1 expression level samples of ACRG (A) and TCGA-STAD (B) cohort (*P < 0.05,**P < 0.01,***P < 0.001).

Figure 6.

GO (A) and KEGG (B) biological process enrichment of LAMB1-related genes.

Figure 7.

Protein-protein interaction (PPI) network of LAMB1-related genes, the top 10 central genes were marked by red.