Identification and Validation of Prognosis-Related Necroptosis Genes for Prognostic Prediction in Hepatocellular Carcinoma

Abstract

Background. The prediction of hepatocellular carcinoma (HCC) survival is challenging because of its rapid progression. In recent years, necroptosis was found to be involved in the progression of multiple cancer types. However, the role of necroptosis in HCC remains unclear. Methods. Clinicopathological parameters and transcriptomic data of 370 HCC patients were obtained from TCGA-LIHC dataset. Prognosis-related necroptosis genes (PRNGs) were identified and utilized to construct a LASSO risk model. The GEO cohorts (GSE54236 and GSE14520) were used for external validation. We evaluated the distribution of HCC patients, the difference in prognosis, and the accuracy of the prognostic prediction of the LASSO risk model. The immune microenvironment and functional enrichment of different risk groups were further clarified. Finally, we performed a drug sensitivity analysis on the PRNGs that constructed the LASSO model and verified their mRNA expression levels in vitro. Results: A total of 48 differentially expressed genes were identified, 23 of which were PRNGs. We constructed the LASSO risk model using nine genes: SQSTM1, FLT3, HAT1, PLK1, MYCN, KLF9, HSP90AA1, TARDBP, and TNFRSF21. The outcomes of low-risk patients were considerably better than those of high-risk patients in both the training and validation cohorts. In addition, stronger bile acid metabolism, xenobiotic metabolism, and more active immune cells and immune functions were observed in low-risk patients, and high expressions of TARDBP, PLK1, and FLT3 were associated with greater drug sensitivity. With the exception of FLT3, the mRNA expression of the other eight genes was verified in Huh7 and 97H cells. Conclusions. The PRNG signature provides a novel and effective method for predicting the outcome of HCC as well as potential targets for further research.

Identification of ANGPT2, FLT3, IGF1 and SPP1 related to glycolysis and PI3K/Akt signaling pathway in hepatocellular carcinoma

“…In our study, FLT3 showed a strong positive correlation in autophagy, apoptosis, angiogenesis, and epithelial-mesenchymal transition-related scores. Previous studies have been shown that FLT3 was involved in the interaction of focal death, apoptosis and necrotic apoptosis in HCC [30]. FLT3 has the strongest positive correlation with the autophagy related gene PRKCB.…”

Identification of necroptosis‐related genes in ankylosing spondylitis by bioinformatics and experimental validation

“…Many population‐based studies have found AS as a risk factor for Parkinson's disease, with a significantly higher prevalence of Alzheimer's among AS patients, 61,62 which agrees with the GSEA analysis findings in the current study. Moreover, recent studies identified that TARDBP would be a novel NRG in the tumour microenvironment 63,64 . However, studies correlating TARDBP with AS are rare, and the role of TARDBP in AS requires further experimental studies.…”

“…Moreover, recent studies identified that TARDBP would be a novel NRG in the tumour microenvironment. 63,64 However, studies correlating TARDBP with AS are rare, and the role of TARDBP in AS requires further experimental studies.…”

Machine learning-based prognostic modeling of lysosome-related genes for predicting prognosis and immune status of patients with hepatocellular carcinoma

“…This resulted in 46 genes with prognostic significance, which were used for further analysis. A common method for constructing models in previous studies was the Lasso method (19,20). In previous studies, the Lasso method was commonly used to construct models, but we found that this may not be the best approach for our data (21).…”