A Risk Model Developed Based on Necroptosis Predicts Overall Survival for Hepatocellular Carcinoma and Identification of Possible Therapeutic Drugs

• DOI: 10.3389/fimmu.2022.870264
• Publication Date: 2022-03-30T04:07:41Z
• Authors: Zedong Li; Jianyu Fang; Sheng Chen; Hao Liu; Jun Zhou; Jiangsheng Huang; Sushun Liu; Yu Peng
• Keywords: 0301 basic medicine; Carcinoma, Hepatocellular; Immunology; Liver Neoplasms; gemcitabine; regulated cell death; necroptosis; TOP2A; hepatocellular carcinoma; RC581-607; 3. Good health; 03 medical and health sciences; Necroptosis; Biomarkers, Tumor; Cytokines; Humans; Immunologic diseases. Allergy

Necroptosis is a form of regulatory cell death (RCD) that attracts and activates immune cells, resulting in pro-tumor or anti-tumor effects. The purpose this study was to investigate genes associated with necroptosis, construct risk score for predicting overall survival patients hepatocellular carcinoma, find potentially effective drugs.The three algorithms ssGSEA, EPIC, ESTIMATE were used quantify the infiltration samples, differentially expressed (DEGs) analysis, weighted gene co-expression network analysis screen necroptosis related genes. Variables screened according random forest combinations significant p-values low number defined as prognostic signatures by using log-rank test after combination. Based on sensitivity data PRISM CTRP2.0 datasets, we predicted potential therapeutic agents high-NRS patients.Seven such TOP2A define necroptosis-related (NRS). value further validated, where high NRS identified poor factor tended have higher grades histologic grade, pathologic stage, T BCLC, CLIP, AFP. Higher also negatively correlated abundance DCs, Neutrophils, Th17 Macrophages, Endothelial, positively Th2 cells. often accompanied release multiple cytokines, found some cytokines significantly both suggesting may affect cells through cytokines. In addition, TP53 mutations more common samples NRS, these be changes NRS. Patients sensitive gemcitabine, gemcitabine an drug improve prognosis which play role inhibiting expression TOP2A.We constructed scoring model predict OS HCC patients, response, mutation, clinical classification patients.