Department of Pharmacy, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, China.
The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Anhui Province Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Institute for Liver Disease, Anhui Medical University, Hefei, Anhui, China.
PeerJ. 2023 Jan 12;11:e14691. doi: 10.7717/peerj.14691. eCollection 2023.
Currently, the most predominant type of liver cancer is hepatocellular carcinoma (HCC), which is also the fourth leading cause of cancer-related death in the global population. Pyroptosis is an emerging form of cell death that affects the prognosis of cancer patients by modulating tumor cell migration, proliferation and invasion. However, the evaluation of pyroptosis in the prognosis of HCC is still insufficient.
A total of 365 HCC patients from the TCGA-LIHC cohort were classified into two distinct subtypes using consensus clustering of pyroptosis-related genes (PRGs). Following univariate Cox analysis of differentially expressed genes between subtypes, we established a prognostic model (PRGs-score, PRGS) by LASSO Cox analysis. We further tested the predictive power of the prognostic model in the ICGC (LIRI-JP) and GEO (GSE14520) cohorts. The tumor microenvironment (TME) was studied using the CIBERSORT. The enrichment scores for immune cells and immune functions in low- and high-PRGS groups were assessed using ssGSEA. The IMvigor210 cohort was used to investigate the immunotherapy efficacy. Furthermore, we validated the expression of prognostic genes in PRGS by RT-qPCR .
The subtyping of HCC based on PRGs exhibited distinct clinical characteristics. We developed a prognostic model PRGS by differentially expressed genes between different subtypes. The results showed that PRGS could well forecast the survival of HCC patients in different cohorts and was associated with the immune microenvironment. Moreover, PRGS was considered to be an independent prognostic risk factor and superior to other pyroptosis-related signatures. Low-PRGS implied greater immune cell infiltration and better overall survival with immunotherapy. The results of RT-qPCR also showed that prognostic genes were significantly dysregulated in HCC.
PRGS has promising application in forecasting the prognosis of HCC patients, and its relationship with the immune microenvironment provides a basis for the subsequent treatment and research of HCC.
目前，最主要的肝癌类型是肝细胞癌（HCC），也是全球癌症相关死亡的第四大原因。细胞焦亡是一种新兴的细胞死亡形式，通过调节肿瘤细胞迁移、增殖和侵袭，影响癌症患者的预后。然而，细胞焦亡在 HCC 预后中的评估仍然不足。
使用与细胞焦亡相关基因（PRGs）一致聚类的方法，对 TCGA-LIHC 队列中的 365 名 HCC 患者进行了两种不同亚型的分类。对亚组间差异表达基因进行单因素 Cox 分析后，我们通过 LASSO Cox 分析建立了一个预后模型（PRGs-score，PRGS）。我们进一步在 ICGC（LIRI-JP）和 GEO（GSE14520）队列中测试了该预后模型的预测能力。使用 CIBERSORT 研究肿瘤微环境（TME）。使用 ssGSEA 评估低和高 PRGS 组中免疫细胞和免疫功能的富集分数。使用 IMvigor210 队列研究免疫治疗的疗效。此外，我们通过 RT-qPCR 验证了 PRGS 中预后基因的表达。
基于 PRGs 的 HCC 亚分型表现出明显的临床特征。我们通过不同亚组间差异表达基因建立了预后模型 PRGS。结果表明，PRGS 可以很好地预测不同队列中 HCC 患者的生存情况，与免疫微环境相关。此外，PRGS 被认为是独立的预后危险因素，优于其他细胞焦亡相关特征。低 PRGS 意味着更多的免疫细胞浸润和更好的总生存率，以及免疫治疗。RT-qPCR 的结果也表明，预后基因在 HCC 中明显失调。
PRGS 在预测 HCC 患者的预后方面具有广阔的应用前景，其与免疫微环境的关系为 HCC 的后续治疗和研究提供了依据。
