Research Paper Volume 14, Issue 23 pp 9699—9714

Establishing a signature based on immunogenic cell death-related gene pairs to predict immunotherapy and survival outcomes of patients with hepatocellular carcinoma

Jianying Ma1, *, , Lianghong Kuang2, *, , Rong Zhao3, ,

  • 1 Department of Breast Surgery, Thyroid Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei 435000, People’s Republic of China
  • 2 Department of Neurology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei 435000, People’s Republic of China
  • 3 Department of Anesthesiology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei 435000, People’s Republic of China
* Equal contribution

Received: August 17, 2022       Accepted: November 23, 2022       Published: December 14, 2022      

https://doi.org/10.18632/aging.204419
How to Cite

Copyright: © 2022 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Immunogenic cell death (ICD) is a type of regulated cell death (RCD) triggered by various stresses that are involved in activating the immune system against cancer in immunocompetent hosts. However, no previous study has investigated the regulation of ICD-related gene pairs involved in hepatocellular carcinoma (HCC). A prognostic signature composed of 8 ICD-related gene pairs was generated that was capable of reliably separating patients with HCC into low- and high-risk subgroups with differing overall survival rates. Significant correlations were observed between risk score and surgical procedure, vascular tumor cell type, recurrence status, tumor status, and stages. The risk score was confirmed to be an independent prognostic factor for HCC and subsequently was employed to construct a prognostic nomogram. Low-risk patients were characterized by higher levels of immune cell infiltration, lower stromal and immune scores, higher tumor purity, higher expression of most immune checkpoints, and higher tumor mutational burden (TMB), revealing different levels of immunological functional pathways between different risk HCC patient cohorts. Furthermore, immunophenoscore (IPS) and Tumor Immune Dysfunction and Exclusion (TIDE) scores demonstrated that patients in the low-risk group are more likely to be sensitive to immunotherapy. In conclusion, the signature conducted by ICD-related gene pairs is a promising biomarker for the prediction of HCC patient outcomes and immunotherapeutic responses.

Abbreviations

ICD: immunogenic cell death; RCD: regulated cell death; HCC: hepatocellular carcinoma; TME: tumor microenvironment (TME); TMB: tumor mutational burden; IPS: immunophenoscore; TIDE: Tumor Immune Dysfunction and Exclusion; ICIs: immune checkpoint inhibitors; DAMPs: damage-associated molecular patterns; PRRs: pattern recognition receptors; DCs: immature dendritic cells; ROC: receiver operator characteristic; AUC: area under the curve; DCA: decision-curve analysis.