Construction of a Necroptosis-Associated Long Non-Coding RNA Signature to Predict Prognosis and Immune Response in Hepatocellular Carcinoma

Abstract

Background: Necroptosis is a form of programmed cell death, and studies have shown that long non-coding RNA molecules (lncRNAs) can regulate the process of necroptosis in various cancers. We sought to screen lncRNAs associated with necroptosis to predict prognosis and tumor immune infiltration status in patients with hepatocellular carcinoma (HCC).Methods: Transcriptomic data from HCC tumor samples and normal tissues were extracted from The Cancer Genome Atlas database. Necroptosis-associated lncRNAs were obtained by co-expression analysis. Necroptosis-associated lncRNAs were then screened by Cox regression and least absolute shrinkage and selection operator methods to construct a risk model for HCC. The models were also validated and evaluated by Kaplan-Meier analysis, univariate and multivariate Cox regression, and time-dependent receiver operating characteristic (ROC) curves. In addition, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment, gene set enrichment, principal component, immune correlation, and drug sensitivity analyses were applied to assess model risk groups. To further differentiate the immune microenvironment of different HCC subtypes, the entire dataset was divided into three clusters, based on necroptosis-associated lncRNAs, and a series of analyses performed.Results: We constructed a model comprising four necroptosis-associated lncRNAs: POLH-AS1, DUXAP8, AC131009.1, and TMCC1-AS1. Overall survival (OS) duration was significantly longer in patients classified as low-risk than those who were high-risk, according to our model. Univariate and multivariate Cox regression analyses further confirmed risk score stability. The analyzed models had area under the ROC curve values of 0.786, 0.713, and 0.639 for prediction of 1-, 3-, and 5-year OS, respectively, and risk score was significantly associated with immune cell infiltration and ESTIMATE score. In addition, differences between high and low-risk groups in predicted half-maximal inhibitory concentration values for some targeted and chemical drugs, providing a potential basis for selection of treatment approach. Finally, cluster analysis facilitated more refined differentiation of the immune microenvironment in patients with HCC and may allow prediction of the effectiveness of immune checkpoint inhibitors.Conclusions: This study contributes to understanding of the function of necroptosis-related lncRNAs in predicting the prognosis and immune infiltration status of HCC. The risk model constructed and cluster analysis provide a basis for predicting the prognosis of patients with HCC and to inform the selection of immunotherapeutic strategies.

Identification and validation of cuproptosis-related LncRNA signatures as a novel prognostic model for head and neck squamous cell cancer

“…Of the seven CRLs in our study, MIR9-3HG, POLH-AS1, and WDFY3-AS2 are reported to play important roles in various cancers by regulating ferroptosis [ 31 – 33 ]. Additionally, POLH-AS1 was identified to regulate the process of necroptosis in hepatocellular carcinoma [ 34 ]. It was also reported that MIR9-3HG knockdown inhibited cell proliferation and promoted apoptosis in cervical cancer [ 35 ].…”

Prognostic signature constructed of seven ferroptosis related lncRNAs predicts the prognosis of HBV related HCC

“…And functional studies indicated that LINC00942 confers chemoresistance to GC cells by impairing apoptosis and inducing stemness (14). Previous researches have proven that AC131009.1 and were associated with necroptosis, suggesting that they play roles in different ways of programmed cell death (15). AC090772.3 was found to be highly expressed in the HCC as a ceRNA related to hypoxia(16) and more in-depth research about AC090772.3 is needed in the future.…”

Anoikis-Related LncRNA Signature Predicts Prognosis and Is Associated With Immune Infiltration in Hepatocellular Carcinoma

“…AL031985.3 is associated with liver cancer ferroptosis, cuproptosis, pyroptosis, and autophagy-related prognosis models[28-30], while AC026412.3 is included in the model predicting copper mortality and focal mortality in hepatocellular carcinoma [31,32]. MKLN1-AS and TMCC1-AS1 are also part of liver cancer-related models such as pyroptosis, ferroptosis, autophagy, necroptosis, and autophagy, respectively [29,31,[33][34][35]. Collectively, the identi ed lncRNAs may be closely related to liver cancer apoptosis and may offer new avenues for targeted therapy.…”