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

Ze-Kun Liu; Ke-Fei Wu; Ren-Yu Zhang; Ling-Min Kong; Run-Ze Shang; Jian-Jun Lv; Can Li; Meng Lu; Yu-Le Yong; Cong Zhang; Nai-Shan Zheng; Yan-Hong Li; Zhi-Nan Chen; Huijie Bian; Ding Wei

doi:10.3389/fonc.2022.794034

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

Front Oncol. 2022 Mar 3:12:794034. doi: 10.3389/fonc.2022.794034. eCollection 2022.

Authors

Ze-Kun Liu¹, Ke-Fei Wu¹, Ren-Yu Zhang¹, Ling-Min Kong¹, Run-Ze Shang², Jian-Jun Lv¹, Can Li¹, Meng Lu¹, Yu-Le Yong¹, Cong Zhang¹, Nai-Shan Zheng¹, Yan-Hong Li³, Zhi-Nan Chen¹, Huijie Bian¹, Ding Wei¹

Affiliations

¹ National Translational Science Center for Molecular Medicine, Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China.
² Department of General Surgery, Affiliated Haixia Hospital of Huaqiao University (The 910 Hospital of the Joint Logistics Team), Quanzhou, China.
³ Department of Gynaecology and Obstetrics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Abstract

Pyroptosis is an inflammatory form of programmed cell death that is involved in various cancers, including hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) were recently verified as crucial mediators in the regulation of pyroptosis. However, the role of pyroptosis-related lncRNAs in HCC and their associations with prognosis have not been reported. In this study, we constructed a prognostic signature based on pyroptosis-related differentially expressed lncRNAs in HCC. A co-expression network of pyroptosis-related mRNAs-lncRNAs was constructed based on HCC data from The Cancer Genome Atlas. Cox regression analyses were performed to construct a pyroptosis-related lncRNA signature (PRlncSig) in a training cohort, which was subsequently validated in a testing cohort and a combination of the two cohorts. Kaplan-Meier analyses revealed that patients in the high-risk group had poorer survival times. Receiver operating characteristic curve and principal component analyses further verified the accuracy of the PRlncSig model. Besides, the external cohort validation confirmed the robustness of PRlncSig. Furthermore, a nomogram based on the PRlncSig score and clinical characteristics was established and shown to have robust prediction ability. In addition, gene set enrichment analysis revealed that the RNA degradation, the cell cycle, the WNT signaling pathway, and numerous immune processes were significantly enriched in the high-risk group compared to the low-risk group. Moreover, the immune cell subpopulations, the expression of immune checkpoint genes, and response to chemotherapy and immunotherapy differed significantly between the high- and low-risk groups. Finally, the expression levels of the five lncRNAs in the signature were validated by quantitative real-time PCR. In summary, our PRlncSig model shows significant predictive value with respect to prognosis of HCC patients and could provide clinical guidance for individualized immunotherapy.

Keywords: hepatocellular carcinoma; immune infiltration; immunotherapy; long non-coding RNA; pyroptosis.