Background Noncoding RNAs (ncRNAs), pyroptosis and tumours are all hot topics in current research, but there are very limited studies on pyroptosis and its regulated ncRNAs in colon adenocarcinoma (COAD). Methods The COAD transcription profile dataset from TCGA was used for differential expression analysis. Pyroptosis-related genes (PRGs), the top 200 long noncoding RNAs (lncRNAs) and circular RNA (circRNAs) were selected from the results to construct an endogenous competitive RNA (ceRNA) network. Moreover, the expression of the ceRNAs was used for consensus cluster analysis of COAD and developing a risk model after combining clinical follow-up data by the least absolute shrinkage and selection operator method. The stability and independent prognostic ability of the risk model were evaluated. Finally, gene set enrichment analysis (GSEA) and immune score comparisons between the high-risk and low-risk groups were performed. Results There were 87 PRGs with significant differences, among which casp3/8, NLRP1/3, and IL-1α/1β were at the core of the interactions. The ceRNA network consisted of 58 lncRNAs, 6 circRNAs, 25 PRGs, and 55 microRNAs. We speculated that KCNQ1OT1-miRNAs-SQSTM1 and HSA_CIRC_0001495-miRNAs-PTEN have great potential and value in the pyroptosis mechanism of COAD. Nine RNAs were involved in the risk score, which had excellent independent prognostic ability. Survival analyses were significant between the high-risk (HR) and low-risk (LR) groups (training cohort: P < 0.001; test cohort: P = 0.037). GSEA was mainly enriched in tumour proliferation and metastasis related pathways, while differences in immune activity showed a bipolar distribution between the HR and LR groups. Conclusions The overall mechanism of pyroptosis in COAD was revealed. CeRNAs most closely related to the pyroptosis mechanism of COAD were selected and used to develop a prognostic model. The results may present new regulatory sites and potential targets for COAD pyroptosis mechanisms.
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