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Research Paper

Identification of an immune subtype predicting survival risk and immune activity in hepatocellular carcinoma

Feng Zhao1,2, Nuo Xu3, Jiali Yang2, Bo Li2, Jianwei Shi1,4, Yuanyuan Zheng1, Longjin Xu5
  • 1Department of Central Laboratory, Huaian Tumor Hospital and Huaian Hospital of Huaian, Huaian 223200, Jiangsu, China
  • 2Department of Interventional Radiology, Huaian Tumor Hospital and Huaian Hospital of Huaian, Huaian 223200, Jiangsu, China
  • 3Queen Mary University of Nanchang, Nanchang 330031, Jiangxi, China
  • 4Department of Ultrasonography, Huaian Tumor Hospital and Huaian Hospital of Huaian, Huaian 223200, Jiangsu, China
  • 5Toxicology and Functional Laboratory, Shandong Center for Disease Control and Prevention, Jinan 250014, Shandong, China
Received: December 29, 2020Accepted: March 23, 2021Published: May 3, 2021
https://doi.org/10.18632/aging.202953

Copyright: © 2021 Zhao 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

Immune checkpoint inhibitors (ICI) prolong the survival for advanced/metastatic patients with lung cancer or melanoma; however, for hepatocellular carcinoma (HCC) patients, a durable response has not been reported. Herein, we used a total of 719 HCC patients with public genomic data to determine potential prognostic and immunogenic subtypes. The non-negative matrix factorization (NMF) method was applied to identify the immune classes and potential subtypes. The proportion of tumor infiltration immune cells was estimated using the CIBERSORT algorithm. Gene set enrichment analysis (GSEA) was utilized to calculate the dysregulated pathways. By using NMF analysis for the gene expression profile of the top immune genes, one HCC subtype with better survival (i.e., low-risk subtype) and another with worse survival (i.e., high-risk subtype) were identified in 3 HCC cohorts (all P < 0.05). Better immune cell infiltration, increased enrichment of immune signatures, higher expression of checkpoints, and elevated tumor mutation load (TML) were significantly enriched in the low-risk subtype (all P < 0.05). Higher mutation rates of immune response genes (e.g., TP53 and MUC16) were also observed in the low-risk subtype (both P < 0.05). Discovery of the HCC low-risk subtype might provide clues for HCC prognosis and immunotherapy prediction.