Identification and Validation of a Necroptosis-related Gene based Prognostic Signature for Patients with Hepatocellular Carcinoma

Abstract Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, nevertheless, its prognostic prediction remains obscure. Necroptosis is a tightly regulated form of cell death, which has been recently reported to be involved in HCC. However, the prognostic value of necroptosis-related genes (NRGs) in HCC has not been reported. In the present study, 159 NRGs of HCC subjects from the Cancer Genome Atlas (TCGA) cohort were downloaded and investigated. Of which, a total of thirty-six NRGs were identified to be significantly differentially expressed. Through univariate and multivariate Cox proportional regression analysis, four NRGs (HSP90AA1, PPIA, SQSTM1 and USP21) were found to have the excellent prognostic capacity for HCC, which could clearly divide patients into high-risk and low-risk groups. Survival analysis showed that the overall survival of high-risk patients was significantly shorter than that of low-risk patients. The independent prognostic value of necroptosis-related features was further confirmed by Cox regression analysis, and the area under the receiver operating characteristic curve of the panel comprising HSP90AA1, PPIA, SQSTM1 and USP21 was 0.807. Furthermore, the prognostic value of these NRGs was verified in another cohort of HCC patients from the ICGC database. Herein, this study shows that a novel necroptosis-related gene signature could be developed for prognostic prediction of HCC in future, which may also provide insights into the prevention and treatment of this disease clinically.