Necroptosis-Related Genes Signatures Identified Molecular Subtypes and Underlying Mechanisms in Hepatocellular Carcinoma

Background: Although emerging evidence supports the relationship between necroptosis (NEC) related genes and hepatocellular carcinoma (HCC), the contribution of these necroptosis-related genes to the development, prognosis, and immunotherapy of HCC is unclear. Methods: The expression of genes and relevant clinical information were downloaded from TCGA- LIHC, LIRI-JP, GSE14520/ NCI, GSE36376, GSE76427, GSE20140, GSE27150, and IMvigor210 datasets. Next, we used an unsupervised clustering method to assign the samples into phenotype clusters base on 15 necroptosis-related genes. Subsequently, we constructed a NEC score based on NEC phenotype-related prognostic genes to quantify the necroptosis related subtypes of individual patients. Results: We divided the samples into the high and low NEC score groups, and the high NEC score showed a poor prognosis. Simultaneously, NEC score is an effective and stable model and had a good performance in predicting the prognosis of HCC patients. A high NEC score was characterized by activation of the stroma and increased levels of immune infiltration. A high NEC score was also related to low expression of immune checkpoint molecules (PD-1/PD-L1). Importantly, the established NEC score would contribute to predicting the response to anti-PD-1/L1 immunotherapy. Conclusions: Our study provide a comprehensive analysis of necroptosis-related genes in HCC. Stratification based on the NEC score may enable HCC patients to benefit more from immunotherapy and help identify new cancer treatment strategies.

Automated summary

In this study, we conducted a comprehensive analysis of necroptosis-related genes in HCC and found that the NEC score can be effectively used to predict the prognosis of HCC patients and is associated with the response to immunotherapy.