A necroptosis -related signature for predicting prognosis and immunotherapy in hepatocellular carcinoma

Background: Hepatocellular Carcinoma (HCC) is an aggressive tumor with an inferior prognosis. Necroptosis is a new form of programmed death that plays a dual effect on the tumor. However, the role of necroptosis-related genes(NRGs) in HCC remains unknown. Methods: All datasets were downloaded from publicly available databases. The consensus clustering analysis was used to classify patients into different subtypes based on NRGs. The Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression were used to develop a prognostic signature. Tumor Immune Dysfunction and Exclusion (TIDE) was used to predict immunotherapy response. Results: The genetic and transcriptional changes of NRGs were observed in HCC. Patients were classified into three clusters based on differentially expressed NRGs, of which Cluster-3 had the worst prognosis and the highest immune infiltration. The prognostic signature was developed based on 8-NRGs, which have shown excellent prognostic performance. The high-risk group in the signature presented significantly higher immune infiltration, such as aDCs, iDCs, macrophages, and Treg, compared to the low-risk group. TMB and immune checkpoints were also higher in the high-risk group. Moreover, a lower TIDE score was observed in the high-risk group, indicating the patients with high risk-score may be suitable for immunotherapy. Via the dataset of IMvigor210, we found a higher risk score in the immunotherapy response group. Conclusion: We developed a new necroptosis-related signature for predicting prognosis with the potential to predict immunotherapy for HCC patients.