ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1589563
This article is part of the Research TopicPANoptosis and its role in T cell-based immunotherapyView all 6 articles
Integrative spatial and single-cell transcriptomics elucidate programmed cell death-driven tumor microenvironment dynamics in hepatocellular carcinoma
Provisionally accepted
Kai Lei1
Yutong Zhao1Shumin Li1Jiawei Liu2Wenhao Chen2Caihong Zhou3
Yi Zhang2Jinmei Tan4Jian Wu1
Qi Zhou1
Jiehui Tan2*- 1The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
- 2Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- 3Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
- 4Wuchuan People's Hospital, Zhanjiang, China
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Purpose: Programmed cell death (PCD) mechanisms play crucial roles in cancer progression and treatment response. This study aims to develop a PCD scores prediction model to evaluate the prognosis of hepatocellular carcinoma (HCC) and elucidate the tumor microenvironment differences.: We analyzed transcriptomic data from 363 HCC patients in the TCGA database and 221 patients in the GEO database to develop a PCD prediction model. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics sequencing (STseq) data from HCC patients were analyzed to investigate the tumor microenvironment and functional disparities. The oncogenic role of the key gene UBE2E1 in the model was explored in HCC through various in vitro experiments.Results: Seventeen PCD-related genes were identified as significant prognostic indicators, forming the basis of our PCD prediction model. High-PCD scores correlated with poorer overall survival (OS) and exhibited significant predictive capabilities.scRNA-seq analysis revealed distinct tumor cell characteristics and immune microenvironment differences between high-and low-PCD groups. High-PCD tumors showed increased cell proliferation and malignancy-associated gene expression. T cells in high-PCD patients were more likely to be exhausted, with elevated expression of exhaustion markers. ST-seq data also confirmed these results. Among the genes associated with the PCD prognostic model, UBE2E1 was identified as a key oncogenic marker in HCC.The PCD prediction model effectively predicts prognosis in HCC patients and reveals critical insights into the tumor microenvironment and immune cell exhaustion. This study underscores the potential of PCD-related biomarkers in guiding personalized treatment strategies for HCC.
Keywords: Hepatocellular Carcinoma, programmed cell death, Prediction model, Tumor Microenvironment, Ube2E1
Received: 07 Mar 2025; Accepted: 24 Jun 2025.
Copyright: © 2025 Lei, Zhao, Li, Liu, Chen, Zhou, Zhang, Tan, Wu, Zhou and Tan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jiehui Tan, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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