Journal of Inflammation Research (Apr 2024)
Construction of an Immunogenic Cell Death-Related Gene Signature and Genetic Subtypes for Predicting Prognosis, Immune Microenvironments, and Drug Sensitivity in Hepatocellular Carcinoma
Abstract
Shuo Li,1,2 Tingyu Zhang,1,2 Xin Sun,1,2 Xiaoke Li1,2 1Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Institute of Liver Diseases, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Xiaoke Li, Beijing University of Chinese Medicine, Haiyuncang 5, Dongcheng District, Beijing, People’s Republic of China, Tel +86 010-84015503, Email [email protected]: Immunogenic cell death (ICD) is a type of regulated cell death that modifies the immune response by releasing DAMPs or danger signals. Herein, we aimed to develop an ICD-related predictive model for patients with hepatocellular carcinoma (HCC) and investigate its applicability for predicting prognostic outcomes and immunotherapeutic responses.Methods: Differentially expressed genes of ICD were identified in the HCC and normal liver samples. A prognostic risk model and a nomogram containing clinicopathological features were created. To validate the effectiveness of the model, an external dataset was used. Clinical characteristics, prognosis, tumor mutation burden, immune microenvironments, biological function and chemotherapeutic drug sensitivity were evaluated for different genetic subtypes and risk groups.Results: A total of 35 ICD-related genes (ICDRGs) were identified between HCC and normal samples, 11 of which were significantly associated with overall survival (OS) in HCC patients. Four different genetic subtypes were formed and eight ICDRGs were selected to develop a risk prognostic model. The risk scores were shown to be an independent prognostic factor for HCC and positively correlated with pathological severity. Patients in the high-risk group had a higher frequency of TP53 mutations, increased expression of immune checkpoints and human leukocyte antigen genes. The inhibitory concentrations of chemotherapeutic drugs differed in different populations.Conclusion: In this study, we developed an ICDRG risk model and demonstrated its applicability in predicting survival outcomes, immune and chemotherapeutic responses in HCC patients. ICDRGs are expected to be used as novel biomarkers in the medical decision-making of HCC.Keywords: immunogenic cell death-related genes, hepatocellular carcinoma, prognosis, immune microenvironments, drug sensitivity
