Identification of a novel immunogenic cell death-related classifier to predict prognosis and optimize precision treatment in hepatocellular carcinoma
Dongjing Zhang,
Bingyun Lu,
Qianqian Ma,
Wen Xu,
Qi Zhang,
Zhiqi Xiao,
Yuanheng Li,
Ren Chen,
An-jiang Wang
Affiliations
Dongjing Zhang
Department of Gastroenterology and Hepatology, Shenzhen Clinical Research Center for Digestive Disease, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
Bingyun Lu
Department of Gastroenterology and Hepatology, Shenzhen Clinical Research Center for Digestive Disease, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
Qianqian Ma
Department of Infectious Diseases, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Wen Xu
Department of Gastroenterology and Hepatology, Shenzhen Clinical Research Center for Digestive Disease, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
Qi Zhang
Department of Gastroenterology and Hepatology, Shenzhen Clinical Research Center for Digestive Disease, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
Zhiqi Xiao
Department of Gastroenterology and Hepatology, Shenzhen Clinical Research Center for Digestive Disease, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
Yuanheng Li
Queen Mary School, Nanchang University, Nanchang, Jiangxi, China
Ren Chen
Department of Infectious Diseases, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China; Corresponding author.crlmczx@163.com
An-jiang Wang
Department of Gastroenterology and Hepatology, Shenzhen Clinical Research Center for Digestive Disease, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China; Corresponding author.
Accumulating studies have highlighted the biological significance of immunogenic cell death (ICD) in cancer immunity. However, the influence of ICD on tumor microenvironment (TME) formation and immune response in Hepatocellular carcinoma (HCC) remains largely unexplored. In this study, we systematically analyzed the mRNA profiles of ICD-related genes in 1847 HCC patients and identified three molecular subtypes with significantly different immune features and prognostic stratification. A reliable risk model named ICD score was constructed via machine learning algorithms to assess the immunological status, therapeutic responses, and clinical outcomes of individual HCC patients. High ICD score indicated an immune-excluded TME phenotype, with lower anticancer immunity and shorter survival time. In contrast, low ICD score corresponded to abundant immune cell infiltration, high sensitivity to immunotherapy and a positive prognosis, indicating an “immune-hot” phenotype. Pan-cancer analysis further validated a negative association between ICD score and the immune cell infiltration levels. In conclusion, our findings revealed that the ICD score could serve as a robust prognostic biomarker to predict the benefits of immunotherapy and optimize the clinical decision-making of HCC patients.
