Analyzing molecular typing and clinical application of immunogenic cell death-related genes in hepatocellular carcinoma

Abstract Background Hepatocellular carcinoma (HCC) is considered one of the most common cancers, characterized by low early detection and high mortality rates, and is a global health challenge. Immunogenic cell death (ICD) is defined as a specific type of regulated cell death (RCD) capable of reshap...

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Main Authors: Cai-Feng Lin, Zhi-Wen Chen, Feng-Ping Kang, Jian-Fei Hu, Long Huang, Cheng-Yu Liao, Jian-Lin Lai, Yi Huang, Zu-Wei Wang, Yi-Feng Tian, Shi Chen
Format: Article
Language:English
Published: BMC 2023-06-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-023-10992-2
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author Cai-Feng Lin
Zhi-Wen Chen
Feng-Ping Kang
Jian-Fei Hu
Long Huang
Cheng-Yu Liao
Jian-Lin Lai
Yi Huang
Zu-Wei Wang
Yi-Feng Tian
Shi Chen
author_facet Cai-Feng Lin
Zhi-Wen Chen
Feng-Ping Kang
Jian-Fei Hu
Long Huang
Cheng-Yu Liao
Jian-Lin Lai
Yi Huang
Zu-Wei Wang
Yi-Feng Tian
Shi Chen
author_sort Cai-Feng Lin
collection DOAJ
description Abstract Background Hepatocellular carcinoma (HCC) is considered one of the most common cancers, characterized by low early detection and high mortality rates, and is a global health challenge. Immunogenic cell death (ICD) is defined as a specific type of regulated cell death (RCD) capable of reshaping the tumor immune microenvironment by releasing danger signals that trigger immune responses, which would contribute to immunotherapy. Methods The ICD gene sets were collected from the literature. We collected expression data and clinical information from public databases for the HCC samples in our study. Data processing and mapping were performed using R software to analyze the differences in biological characteristics between different subgroups. The expression of the ICD representative gene in clinical specimens was assessed by immunohistochemistry, and the role of the representative gene in HCC was evaluated by various in vitro assays, including qRT-PCR, colony formation, and CCK8 assay. Lasso-Cox regression was used to screen prognosis-related genes, and an ICD-related risk model (ICDRM) was constructed. To improve the clinical value of ICDRM, Nomograms and calibration curves were created to predict survival probabilities. Finally, the critical gene of ICDRM was further investigated through pan-cancer analysis and single-cell analysis. Results We identified two ICD clusters that differed significantly in terms of survival, biological function, and immune infiltration. As well as assessing the immune microenvironment of tumors in HCC patients, we demonstrate that ICDRM can differentiate ICD clusters and predict the prognosis and effectiveness of therapy. High-risk subpopulations are characterized by high TMB, suppressed immunity, and poor survival and response to immunotherapy, whereas the opposite is true for low-risk subpopulations. Conclusions This study reveals the potential impact of ICDRM on the tumor microenvironment (TME), immune infiltration, and prognosis of HCC patients, but also a potential tool for predicting prognosis.
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spelling doaj.art-25aaf75054f84788a5a929ce7ac40e492023-06-11T11:16:35ZengBMCBMC Cancer1471-24072023-06-0123112110.1186/s12885-023-10992-2Analyzing molecular typing and clinical application of immunogenic cell death-related genes in hepatocellular carcinomaCai-Feng Lin0Zhi-Wen Chen1Feng-Ping Kang2Jian-Fei Hu3Long Huang4Cheng-Yu Liao5Jian-Lin Lai6Yi Huang7Zu-Wei Wang8Yi-Feng Tian9Shi Chen10Shengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityAbstract Background Hepatocellular carcinoma (HCC) is considered one of the most common cancers, characterized by low early detection and high mortality rates, and is a global health challenge. Immunogenic cell death (ICD) is defined as a specific type of regulated cell death (RCD) capable of reshaping the tumor immune microenvironment by releasing danger signals that trigger immune responses, which would contribute to immunotherapy. Methods The ICD gene sets were collected from the literature. We collected expression data and clinical information from public databases for the HCC samples in our study. Data processing and mapping were performed using R software to analyze the differences in biological characteristics between different subgroups. The expression of the ICD representative gene in clinical specimens was assessed by immunohistochemistry, and the role of the representative gene in HCC was evaluated by various in vitro assays, including qRT-PCR, colony formation, and CCK8 assay. Lasso-Cox regression was used to screen prognosis-related genes, and an ICD-related risk model (ICDRM) was constructed. To improve the clinical value of ICDRM, Nomograms and calibration curves were created to predict survival probabilities. Finally, the critical gene of ICDRM was further investigated through pan-cancer analysis and single-cell analysis. Results We identified two ICD clusters that differed significantly in terms of survival, biological function, and immune infiltration. As well as assessing the immune microenvironment of tumors in HCC patients, we demonstrate that ICDRM can differentiate ICD clusters and predict the prognosis and effectiveness of therapy. High-risk subpopulations are characterized by high TMB, suppressed immunity, and poor survival and response to immunotherapy, whereas the opposite is true for low-risk subpopulations. Conclusions This study reveals the potential impact of ICDRM on the tumor microenvironment (TME), immune infiltration, and prognosis of HCC patients, but also a potential tool for predicting prognosis.https://doi.org/10.1186/s12885-023-10992-2Hepatocellular carcinoma1Immunogenic cell death2Tumor microenvironment3Prognostic model4Immunotherapy5
spellingShingle Cai-Feng Lin
Zhi-Wen Chen
Feng-Ping Kang
Jian-Fei Hu
Long Huang
Cheng-Yu Liao
Jian-Lin Lai
Yi Huang
Zu-Wei Wang
Yi-Feng Tian
Shi Chen
Analyzing molecular typing and clinical application of immunogenic cell death-related genes in hepatocellular carcinoma
BMC Cancer
Hepatocellular carcinoma1
Immunogenic cell death2
Tumor microenvironment3
Prognostic model4
Immunotherapy5
title Analyzing molecular typing and clinical application of immunogenic cell death-related genes in hepatocellular carcinoma
title_full Analyzing molecular typing and clinical application of immunogenic cell death-related genes in hepatocellular carcinoma
title_fullStr Analyzing molecular typing and clinical application of immunogenic cell death-related genes in hepatocellular carcinoma
title_full_unstemmed Analyzing molecular typing and clinical application of immunogenic cell death-related genes in hepatocellular carcinoma
title_short Analyzing molecular typing and clinical application of immunogenic cell death-related genes in hepatocellular carcinoma
title_sort analyzing molecular typing and clinical application of immunogenic cell death related genes in hepatocellular carcinoma
topic Hepatocellular carcinoma1
Immunogenic cell death2
Tumor microenvironment3
Prognostic model4
Immunotherapy5
url https://doi.org/10.1186/s12885-023-10992-2
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