Background. Liver hepatocellular carcinoma (LIHC) is a malignance with high incidence and recurrence. Pyroptosis is a programed cell death pattern which both activates the effective immune response and causes cell damage. However, their potential applications of pyroptosis-related genes (PRGs) in the prognostic evaluation and immunotherapy of LIHC are still rarely discussed. Methods. Comprehensive bioinformatics analyses based on TCGA-LIHC dataset were performed in the current study. Results. A total of 33 PRGs were selected to perform the current study. Of these 33 PRGs, 26 PRGs with upregulation or downregulation in LIHC tissues were identified. We also summarized the related genetic mutation variation landscape. GO and KEGG pathway analysis demonstrated that these 26 PRGs were primarily associated with pyroptosis, positive regulation of interleukin-1 beta production, and NOD-like receptor signaling pathway. An unfavorable OS appeared in LIHC patients with high CASP3, CASP4, CASP6, CASP8, GPX4, GSDMA, GSDME, NLRP3, NLRP7, NOD1, NOD2, PLCG1, and SCAF11 expression and low NLRP6 expression. A prognostic signature constructed by the above 14 prognostic PRGs had moderate to high accuracy to predict LIHC patients’ prognosis. And risk score was correlated with the expression of CASP6, CASP8, GPX4, GSDMA, GSDME, NLRP6, and NOD2. Of these 7 genes, CASP8 was identified as the core gene in PPI network. Moreover, lncRNA MIR17HG/hsa-miRNA-130b-3p/CASP8 regulatory axis in LIHC was also detected. Conclusions. The current study indicated the crucial role of PRGs in the prognostic evaluation of LIHC patients and their correlations with tumor microenvironment in LIHC.
Background. Liver hepatocellular carcinoma (LIHC) ranks the sixth in global cancer incidence with poor prognosis. Necroptosis is a kind of regulated cell death and has been proved to be of significance in cancer occurrence and progression. However, few studies comprehensively discuss the potential applications of necroptosis-related genes (NRGs) in the prognostic evaluation and immunotherapy of LIHC. Methods. The prognostic signature in the present study was built up using LASSO Cox regression analysis. Integrated bioinformatics tools were utilized to explore the potential mRNA-miRNA-lncRNA regulatory axis in LIHC. Furthermore, qRT-PCR method was used to verify the EZH2 expression in LIHC tissues. Furthermore, prognostic performance of EZH2 in LIHC was assessed by Kaplan-Meier method. Results. A total of 14 NRGs were differentially expressed in LIHC tissues. The overall genetic mutation status of these NRGs in LIHC was also shown. NRGs were significantly correlated with programmed necrotic cell death, as well as Toll-like receptor signaling pathway in GO and KEGG pathway analysis. Kaplan-Meier analysis revealed that ALDH2, EZH2, NDRG2, PGAM5, RIPK1, and TRAF2 were related to the prognosis. A prognostic signature was constructed by these six genes and showed medium to high accuracy in the prediction of LIHC patients’ prognosis. Further analysis revealed that NRGs were correlated with pathological stage, immune infiltration, and drug resistance in LIHC. Moreover, we identified a potential lncRNA TUG1/miR-26b-5p/EZH2 regulatory axis in LIHC, which might affect the progression of LIHC. qRT-PCR suggested a higher mRNA level of EZH2 in LIHC tissues. And a poor overall survival rate was detected in LIHC patients with high EZH2 expression. Moreover, EZH2 expression and cancer stage were identified as the independent risk factors affecting LIHC patients’ prognosis. Conclusion. In the present study, we conducted comprehensive bioinformatic analyses and built up a necroptosis-related prognostic signature containing four genes (ALDH2, EZH2, NDRG2, and PGAM5) for patients with LIHC, and this prognostic signature showed a medium to high predictive accuracy. And our study also identified a lncRNA TUG1/miR-26b-5p/EZH2 regulatory axis, which might be of great significance in LIHC progression. In addition, based on the data from our center, the result of qRT-PCR and survival analysis showed a higher mRNA level of EZH2 in LIHC tissues and an unfavorable prognosis in high EZH2 expression group, respectively.
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