Hepatocellular carcinoma (HCC) is an invasive malignant tumor, and pyroptosis makes an important contribution to the pathology and progression of liver cancer. Many prognostic models have been proposed for HCC based on the quantitative expression level of candidate genes, which are unsuitable for clinical application due to their vulnerability against experimental batch effects. The aim of this study was to develop a novel pyroptosis-related long non-coding RNA (lncRNA)-based prognostic index (PLPI) for HCC based on relative expression orderings (REOs).

Firstly, the pyroptosis-related lncRNAs were identified through the Wilcoxon rank-sum test and gene co-expression analyses. Then, the novel prognostic model PLPI was constructed by pyroptosis-related lncRNA pairs, which were identified by multiple machine learning algorithms. Gene set enrichment, somatic mutation, and drug sensitivity analyses were conducted to measure the differences between high- and low-risk patients. Multiple immune analyses were used to explore the association between PLPI and the immunological microenvironment.

In this study, a novel prognostic model PLPI based on 10 pyroptosis-related lncRNA pairs was constructed, which was proven to be an independent prognostic risk factor. The receiver operating characteristic (ROC) curves showed that the model had a good prognostic ability in the training, testing, and external set, respectively [5-year area under the curve (AUC) =0.73, 5-year AUC =0.81, 4-year AUC =0.79]. The results of survival, somatic mutation, and immune analyses showed that the patients in the low-risk group had a better prognosis, lower rates of somatic mutation, and better immune cell infiltration. Personalized chemotherapeutic drugs were also identified for the patients with HCC.

The novel PLPI not only greatly predicted the prognosis of patients with HCC but could also offer novel ideas and approaches for the therapeutic management of HCC.

The tumour microenvironment is a key determinant of the efficacy of immunotherapy. Angiogenesis is closely linked to tumour immunity. We aimed to screen long non-coding ribonucleic acids (lncRNAs) associated with angiogenesis to predict the prognosis of individuals with hepatocellular carcinoma (HCC) and characterise the tumour immune microenvironment (TIME). Patient data, including transcriptome and clinicopathological parameters, were retrieved from The Cancer Genome Atlas database. Moreover, co-expression algorithm was utilized to obtain angiogenesis-related lncRNAs. Additionally, survival-related lncRNAs were identified using Cox regression and the least absolute shrinkage and selection operator algorithm, which aided in constructing an angiogenesis-related lncRNA signature (ARLs). The ARLs was validated using Kaplan-Meier method, time-dependent receiver operating characteristic analyses, and Cox regression. Additionally, an independent external HCC dataset was used for further validation. Then, gene set enrichment analysis, immune landscape, and drug sensitivity analyses were implemented to explore the role of the ARLs. Finally, cluster analysis divided the entire HCC dataset into two clusters to distinguish different subtypes of TIME. This study provides insight into the involvement of angiogenesis-associated lncRNAs in predicting the TIME characteristics and prognosis for individuals with HCC. Furthermore, the developed ARLs and clusters can predict the prognosis and TIME characteristics in HCC, thereby aiding in selecting the appropriate therapeutic strategies involving immune checkpoint inhibitors and targeted drugs.

Currently, the prognosis of hepatocellular carcinoma (HCC) is poor, and there is a lack of effective targeted therapy. As key mediators of the immune response, the prognostic value of antigen-presenting cells (APCs) in HCC still remains unclear. In this study, we aimed to identify APC-related genomic subtypes and develop a novel prognostic model in HCC. Our results indicated that overall survival (OS) and the level of immune infiltration significantly differed between different APC clusters. By analyzing the gene expression profile between APC clusters, APC-related genomic subtypes were identified. There was a significant difference in OS and tumor microenvironment infiltration in HCC patients with different genomic subtypes. With the aid of genomic subtypes, significantly differentially expressed genes were screened to generate a novel prognostic model. The risk score of the model had a significant positive correlation with APCs and was associated with immune checkpoint expressions. Through the clinical cohort collected from the First Affiliated Hospital of Wenzhou Medical University, the prognostic value of the risk score was further validated. Moreover, after the risk score and clinical characteristics were combined, a nomogram was constructed to evaluate the prognosis for HCC patients. In conclusion, we mainly identified the APC-related genomic subtypes and generated a novel prognostic model to improve the prognostic prediction and targeted therapy for HCC patients.