Abstract
Pyroptosis, a novel pro-inflammatory type of programmed cell death, is involved in the tumorigenesis of various cancers. Recent findings have implicated long non-coding RNAs (lncRNAs) in the serial steps of cancer development. However, the expression and prognostic signatures of pyroptosis-related lncRNAs in hepatocellular carcinoma (HCC) remain largely unknown. Therefore, a pyroptosis-related lncRNA prognostic model was constructed for HCC. Thirty-four pyroptosis-related genes were obtained from previous reviews, and gene expression data were collected from The Cancer Genome Atlas (TCGA) database. Spearman's correlation test was used to identify potential pyroptosis-related lncRNAs. Cox and LASSO regression analyses were used to construct a prognostic model. Subsequently, receiver operating characteristic (ROC) curves were constructed to assess the model's predictive ability for the overall survival (OS) of HCC patients. CytoHubba was used to screen out the potential hub gene, whose expression was verified using clinical samples from HCC patients. Finally, nine pyroptosis-related differentially expressed lncRNAs in HCC were identified, and a prognostic model with four pyroptosis-related lncRNAs was constructed with an area under the ROC curve (AUC) of approximately 0.734. Single-sample gene set enrichment analysis and TCGA revealed different immune infiltration and immune checkpoints between the two risk groups. Moreover, these lncRNAs are closely related to the pyroptosis-related gene, NLRP6, which may be considered a hub gene. NLRP6 was lower-expressed in HCC samples, and patients with lower expression of NLRP6 had the longer OS. In conclusion, NLRP6-dependent pyroptosis-related lncRNAs play important roles in tumor immunity and may be potential predictors and therapeutic targets for HCC.
Highlights
Hepatocellular carcinoma (HCC), the main type of primary liver cancer, is the second leading cause of cancer-related deaths worldwide [1]
Six upregulated Long non-coding RNAs (lncRNAs) correlated with poor overall survival (OS) were considered potential prognostic biomarkers for hepatocellular carcinoma (HCC) patients, while three downregulated lncRNAs (TMEM220-AS1, AC015908.3, and AP001065.3) were correlated with more favorable OS
We suggest that lncRNAs included in our prognosis model participate in tumor development by regulating the NLRP6dependent pyroptosis pathway
Summary
Hepatocellular carcinoma (HCC), the main type of primary liver cancer, is the second leading cause of cancer-related deaths worldwide [1]. The conventional clinical curative options for HCC are surgical resection, tumor ablation, arterial catheterbased treatment, liver transplantation, and recently, targeted therapeutic agents such as sorafenib, which are used for advanced HCC patients. There is an urgent need to explore useful prognostic biomarkers and therapeutic targets for patients with HCC. Pan et al found that the lncRNA PDPK2P could interact with PDK1 to promote HCC progression via the PDK1/AKT/caspase-3 signaling pathway [8]. Ni et al [9] reported that a novel lncRNA uc.134 may repress HCC progression by regulating post-translational modifications, including phosphorylation and ubiquitination of LATS1 and YAPS127 to inhibit YAP and activate Hippo kinase signaling. It is believed that large-scale screening accompanied with validation experiments could propose highly specific lncRNAs as clinical diagnostic, prognostic, and potential therapeutic biomarkers
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