The Pyroptosis-Related Gene Signature Predicts the Prognosis of Hepatocellular Carcinoma

Abstract

Objective: Hepatocellular carcinoma (HCC) is a genetically and phenotypically heterogeneous tumor, and the prediction of its prognosis remains a challenge. In the past decade, studies elucidating the mechanisms that induce tumor cell pyroptosis has rapidly increased. The elucidation of their mechanisms is essential for the clinical development optimal application of anti-hepatocellular carcinoma therapeutics.Methods: Based on the different expression profiles of pyroptosis-related genes in HCC, we constructed a LASSO Cox regression pyroptosis-related genes signature that could more accurately predict the prognosis of HCC patients.Results: We identified seven pyroptosis-related genes signature (BAK1, CHMP4B, GSDMC, NLRP6, NOD2, PLCG1, SCAF11) in predicting the prognosis of HCC patients. Kaplan Meier survival analysis showed that the pyroptosis-related high-risk gene signature was associated with poor prognosis HCC patients. Moreover, the pyroptosis-related genes signature performed well in the survival analysis and ICGC validation group. The hybrid nomogram and calibration curve further demonstrated their feasibility and accuracy for predicting the prognosis of HCC patients. Meanwhile, the evaluation revealed that our novel signature predicted the prognosis of HCC patients more accurately than traditional clinicopathological features. GSEA analysis further revealed the novel signature associated mechanisms of immunity response in high-risk groups. Moreover, analysis of immune cell subsets with relevant functions revealed significant differences in aDCs, APC co-stimulation, CCR, check-point, iDCs, Macrophages, MHC class-I, Treg, and type II INF response between high- and low-risk groups. Finally, the expression of Immune checkpoints was enhanced in high-risk group, and m6A-related modifications were expressed differently between low- and high-risk groups.Conclusion: The novel pyroptosis-related genes signature can predict the prognosis of patients with HCC and insight into new cell death targeted therapies.

Identification and Validation of Two Heterogeneous Molecular Subtypes and a Prognosis Predictive Model for Hepatocellular Carcinoma Based on Pyroptosis

“…Besides, we constructed a novel multigene predictive model for HCC patients and validated the model genes' expression differences through several different analyses. Recently, some similar studies about different PRG research in HCC subtype identification [40][41][42][43][44][45][46] and predictive model construction [40][41][42][43][44][45][46][47][48][49] have been published. However, in all the previous subtype identification studies, the cluster analyses were conducted only in one cohort while we also tested in a validation cohort.…”

“…Moreover, the association between the pyroptosis pattern and other features of the subtypes were not elucidated. In the predictive model construction studies, most of them did not perform expression validation for the model genes [41][42][43][44][45][46][47][48]. In a word, we have conducted in-depth analyses for the molecular subtypes and validated the mode genes' expression by various analyses which makes our results more reliable and practical in HCC clinical application as well as its future research.…”

A Multi-Omics Analysis of NASH-Related Prognostic Biomarkers Associated with Drug Sensitivity and Immune Infiltration in Hepatocellular Carcinoma

“…In the test set, the high- and low-risk groups exhibited significantly different survival probabilities ( p = 0.008) with an AUC of 0.780, 0.726, and 0.699 in a time-dependent ROC at one, three, and five years ( Figure 4 D–F). In addition, the prognostic model constructed based on our risk score was superior to the single gene ( Figure 4 G–I) and other models that have been published [ 21 , 22 , 23 , 24 ].…”

A Novel Defined Pyroptosis-Related Gene Signature for Predicting the Prognosis of Endometrial Cancer

“…Ye et al [ 12 ] showed a novel signature of seven PRGs (AIM2, PJVK, PLCG1, GSDMA, ELANE, CASP3, and CASP6) for predicting the prognosis of ovarian cancer (OC). Zhang et al [ 22 ] identified a new signature featuring seven PRGs (BAK1, CHMP4B, NOD2, NLRP6, GSDMC, PLCG1, and SCAF11) in predicting the prognosis of hepatocellular carcinoma (HCC) patients. Chen et al [ 14 ] constructed eight-PRG signature (AIM2, BAK1, GZMA, GZMB, IRF1, NOD2, TNF, and TP63) to predict the survival in bladder cancer (BC) patients.…”