Development and Validation of a Pyroptosis-Related Signature for Predicting Prognosis in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) has emerged as a primary health problem and threat to global mortality, especially in China. Since pyroptosis as a new field for HCC prognosis is not well studied, it is important to open a specific prognostic model. In this study, consensus clustering method for 42 pyroptosis-related genes to classify 374 HCC patients in the TCGA database. After cox regression analysis of the differentially expressed genes between the two clusters, LASSO-Cox analysis was then performed to construct a pyroptosis-related prognostic model with 11 genes including MMP1, KPNA2, LPCAT1, NEIL3, CDCA8, SLC2A1, PSRC1, CBX2, HAVCR1, G6PD, MEX3A. The ICGC dataset was served as the validation cohort. Patients in the high-risk group had significantly lower overall survival (OS) rates than those in the low-risk group (p < 0.05). COX regression analysis showed that our model could be used as an independent prognostic factor to predict prognosis of patients and was significantly correlated with clinicopathological characteristics. Nomogram showing the stability of the model predicting the 1, 3, 5 year survival probability of patients. In addition, based on the risk model, ssGSEA analysis revealed significant differences in the level of immune cell infiltration and activation of immune-related functional pathways between high and low-risk groups, and patients with the high-risk score may benefit more from treatment with immune checkpoint inhibitors. Furthermore, patients in the high-risk group were more tend to develop chemoresistance. Overall, we identified a novel pyroptosis-related risk signature for prognosis prediction in HCC patients and revealed the overall immune response intensity of the tumor microenvironment. All these findings make the pyroptosis signature shed light upon a latent therapeutic strategy aimed at the treatment and prevention of cancers.

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 Comprehensive Analysis of Pyroptosis-Related lncRNAs Signature Associated With Prognosis and Tumor Immune Microenvironment of Pancreatic Adenocarcinoma

“…According to the previous research, a total of 52 pyroptosis-related genes (PRGs) were gathered for our exploration ( Supplementary Table S1 ) ( Wang et al, 2021 ; Ding et al, 2022 ). The lncRNA list was distinguished from the gene expression matrix based on the GTF annotation files by Perl language.…”

Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma

“…Patients with advanced metastatic and/or recurrent HCCs have failed to gain benefit over the long term from standard HCC treatments such as surgical resection and liver transplantation (3). Therefore, it is crucial to explore novel molecularly-targeted therapies and new prognostic factors for HCC patients (4)(5)(6). Very, recently, multiple personalized molecular subtypes of HCC have been reported.…”