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Published on: March 14, 2019
A Novel Pyroptosis-Associated Gene Signature to Predict Prognosis in Patients with Colorectal Cancer
Juji Dai1, Shuangdong Chen2, Yongyu Bai3
1Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Ouhai District, Wenzhou, Zhejiang 325000, China.
Background:
Pyroptosis is a form of cell death characterized by cell swelling and plasma membrane bubbling in association with inflammatory and immune responses. To date, the association between pyroptosis and colorectal cancer remains unclear. We aimed to establish a novel pyroptosis-associated model for the prognosis of colorectal cancer.
Methods:
Pyroptosis-related genes were extracted using Gene Set Enrichment Analysis. A least absolute shrinkage and selection operator regression model was constructed to identify a pyroptosis-related gene signature using the Cancer Genome Atlas and Gene Expression Omnibus databases. Then, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology and GSEA were performed to better understand the potential mechanisms and the functional pathways associated with pyroptosis involved in colorectal cancer. The relationship between the pyroptosis-related signature and immune infiltration was investigated using Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts and MCPcounter.
Results:
A 12 pyroptosis-related gene signature was identified. Then, patients were classified into high- and low-risk groups. Kaplan-Meier and receiver operating characteristic analyses confirmed that the high-risk groups showed worse overall survival, progression-free survival, or relapse-free survival probability. Functional enrichment analysis showed that pyroptosis was associated with extracellular matrix-related pathways. Furthermore, the pyroptosis risk score was associated with immune infiltration. The low-risk group exhibited a higher percentage of plasma cells, CD4 T cells, activated dendritic cells, and activated mast cells. M2 macrophages and M0 macrophages were positively related to the risk score.
Conclusion:
Our research yielded a novel pyroptosis-related prognostic signature for colorectal cancer that was related to immune cell infiltration, and it provided an immunological perspective for developing personalized therapies.
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