Characterizing the prognostic and therapeutic value of necroptosis in sarcoma based on necroptosis subtypes.

Abstract

Necroptosis, a type of necrotic cell death independent of caspase regulation, is mainly mediated by receptor interacting serine/threonine kinase 1 (RIPK1), receptor interacting serine/threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL). Necroptosis plays an essential role in many tumors. However, the potential roles of necroptosis in tumor microenvironment (TME) of sarcoma (SARC) remain unknown. This study analyzed the expression, prognosis, genetic alterations of necroptosis genes in SARC. We identified two subtypes (cluster A and B) by performing unsupervised consensus clustering. Cluster A and B greatly differed in prognosis and immune infiltration, with cluster A showing more favorable prognosis, higher immune infiltration and higher expression levels of necroptosis genes than cluster B. Based on the differentially expressed genes (DEGs) between two clusters, a necroptosis scoring system was developed for predicting overall survival of SARC patients. Patients with high necroptosis score had worse survival status, with a decreased infiltration level of most immune cells. Our findings demonstrated the potential role of necroptosis in regulating tumor microenvironment and the prognostic value of necroptosis-related genes for SARC patients.