Identification of PANoptosis-Based Prognostic Signature for Predicting Efficacy of Immunotherapy and Chemotherapy in Hepatocellular Carcinoma

Abstract

Background. PANoptosis has been a research hotspot, but the role of PANoptosis in hepatocellular carcinoma (HCC) remains widely unknown. Drug resistance and low response rate are the main limitations of chemotherapy and immunotherapy in HCC. Thus, construction of a prognostic signature to predict prognosis and recognize ideal patients for corresponding chemotherapy and immunotherapy is necessary. Method. The mRNA expression data of HCC patients was collected from TCGA database. Through LASSO and Cox regression, we developed a prognostic signature based on PANoptosis-related genes. KM analysis and ROC curve were implemented to evaluate the prognostic efficacy of this signature, and ICGC and GEO database were used as external validation cohorts. The immune cell infiltration, immune status, and IC50 of chemotherapeutic drugs were compared among different risk subgroups. The relationships between the signature and the efficacy of ICI therapy, sorafenib treatment, and transcatheter arterial chemoembolization (TACE) therapy were investigated. Result. A 3-gene prognostic signature was constructed which divided the patients into low- and high-risk subgroups. Low-risk patients had better prognosis, and the risk score was proved to be an independent predictor of overall survival (OS), which had a well predictive effect. Patients in high-risk population had more immunosuppressive cells (Tregs, M0 macrophages, and MDSCs), higher TIDE score and TP53 mutation rate, and elevated activity of base excision repair (BER) pathways. Patients with low risk benefited more from ICI, TACE, and sorafenib therapy. The predictive value of the risk score was comparable with TIDE and MSI for OS under ICI therapy. The risk score could be a biomarker to predict the response to ICI, TACE, and sorafenib therapy. Conclusion. The novel signature based on PANoptosis is a promising biomarker to distinguish the prognosis predict the benefit of ICI, TACE, and sorafenib therapy, and forecast the response to them.

Identification of PANoptosis-related biomarkers and analysis of prognostic values in head and neck squamous cell carcinoma

“…In esophageal cancer, PANoptosis mediated by sulconazole could induce oxidative stress and impair aerobic glycolysis to enhance radiosensitivity 21 . Xiong et al identified that PANoptosis might be an important indicator for efficacy of immunotherapy and chemotherapy in hepatocellular carcinoma (HCC) 22 . Wei et al also showed that PANoptosis was associated with HCC overall survival, immune infiltration, and immunotherapy response 23 , suggesting that PANoptosis showed promise to be a therapeutic target.…”

Cell death shapes cancer immunity: spotlighting PANoptosis

“…This conclusive analysis revealed a significant correlation of SNHG7, an lncRNA, with COAD prognosis, tumor stage, lymph node metastasis, and drug resistance [ 106 ]. Reportedly through the construction of a prognostic signature to predict prognosis and recognize ideal patients for corresponding chemotherapy and immunotherapy, it was suggested that risk score could be a biomarker to predict the response to ICIs, TACE, and sorafenib therapy [ 107 ]. There are only few reports on experimental studies that link PANoptosis with drug resistance for antitumor purposes.…”

Analyzing the research landscape: Mapping frontiers and hot spots in anti-cancer research using bibliometric analysis and research network pharmacology

“…In the past few decades, researchers have been devoted to finding drugs to treat cancer and have made tremendous progress in areas such as chemotherapy drugs ( Wang Y. et al, 2023 ), targeted drugs ( Isaksson et al, 2023 ; Jiang et al, 2023 ), immunotherapy ( Ren et al, 2023 ; Xiong et al, 2023 ; Yadav et al, 2023 ), sonodynamic therapy ( Wu et al, 2022 ), and radiation therapy ( Eyre-Walker and Stoletzki, 2013 ; Dumago et al, 2023 ; Moon et al, 2023 ). However, these anti-cancer strategies have shortcomings, including side effects and cancer recurrence.…”