The Risk Signature of Pyroptosis-Related Long Noncoding RNAs Predicts Prognosis and Indicates Immunotherapeutic Efficiency in Hepatocellular carcinoma

Pyroptosis can cause inflammasome activation through Caspase-1/NOD-like receptor 3 (NLRP3) pathways, which is closely related to hepatocellular carcinoma (HCC). The immunotherapy of HCC has a good overall effect and has been widely used in clinical, but the exact effect varies from person to person. Dysregulation of lncRNA can lead to inflammatory and abnormal immune microenvironment in HCC. However, few studies have reported the role for pyroptosis-related lncRNAs (PRlncRNAs) in HCC. In this study, we constructed and validated a risk model based on 8 PRlncRNAs to predict the prognosis of patients and immune cell infiltration in HCC using bioinformatics approaches and experiments. Our risk model showed that patients in a high-risk group exhibited a poor prognosis and risk score is an independent prognostic factor. AUC analysis proved that our risk signature more accurately predicted the prognosis of patients than traditional clinicopathological indexes. The results of GSEA and (ss)GSEA showed that high-risk group genes were mainly enriched in immune pathways and that their executive function depended on inhibitory immune checkpoints. Furthermore, downregulation of AC009283.1 expression accelerated the HCC cells progression, reduced NLRP3/Caspase-1 expression and infiltration of CD3. While si-LINC00942 got the opposite results. Overall, the novel signature has a high credibility in predicting the patient prognosis and evaluating the immune status, which has important significance for guiding immunotherapy and developing precise treatments to benefit HCC patients.