Abstract
Objective: We aimed to explore the prognostic value of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes in gastric cancer (GC). Methods: The RNA-sequencing (RNA-seq) expression data for 351 GC patients and other relevant clinical data were acquired from The Cancer Genome Atlas (TCGA). Survival analysis and a genome-wide gene set enrichment analysis (GSEA) were performed to define the underlying molecular value of the ADAMTS genes in GC development. Besides, qRT-PCR and immunohistochemistry were all employed to validate the relationship between the expression of these genes and GC patient prognosis. Results: The Log rank test with both Cox regression and Kaplan–Meier survival analyses showed that ADAMTS6 expression profile correlated with the GC patients clinical outcome. Patients with a high expression of ADAMTS6 were associated with poor overall survival (OS). Comprehensive survival analysis of the ADAMTS genes suggests that ADAMTS6 might be an independent predictive factor for the OS in patients with GC. Besides, GSEA demonstrated that ADAMTS6 might be involved in multiple biological processes and pathways, such as the vascular endothelial growth factor A (VEGFA), kirsten rat sarcoma viral oncogene (KRAS), tumor protein P53, c-Jun N-terminal kinase (JNK), cadherin (CDH1) or tumor necrosis factor (TNF) pathways. It was also confirmed by immunohistochemistry and qRT-PCR that ADAMTS6 is highly expressed in GC, which may be related to the prognosis of GC patients. Conclusion: In summary, our study demonstrated that ADAMTS6 gene could be used as a potential molecular marker for GC prognosis.
Highlights
Gastric cancer (GC) is the fourth most common cancer and the second cause of mortality worldwide [1]
In determining the potential diagnostic value of ADAMTS family in distinguishing between GC tumor tissue and adjacent normal tissue, the results of unpaired t test showed that ADAMTS1 and ADAMTS8 mRNA expression was down-regulated in GC tumor tissues as compared with the adjacent normal tissues (P
The gene–gene interaction network showed that the ADAMTS genes are strongly co-expressed (Figure 4A), while the PPI network analysis showed that the ADAMTS proteins directly interact with each other (Figure 4B)
Summary
We aimed to explore the prognostic value of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes in gastric cancer (GC). QRT-PCR and immunohistochemistry were all employed to validate the relationship between the expression of these genes and GC patient prognosis. GSEA demonstrated that ADAMTS6 might be involved in multiple biological processes and pathways, such as the vascular endothelial growth factor A (VEGFA), kirsten rat sarcoma viral oncogene (KRAS), tumor protein P53, c-Jun N-terminal kinase (JNK), cadherin (CDH1) or tumor necrosis factor (TNF) pathways. It was confirmed by immunohistochemistry and qRT-PCR that ADAMTS6 is highly expressed in GC, which may be related to the prognosis of GC patients. Accepted Manuscript online: 14 April 2021 Version of Record published: 22 April 2021
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