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Updated: Aug 9, 2025
Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
Published on: April 12, 2024
HAMP as a Potential Diagnostic, PD-(L)1 Immunotherapy Sensitivity and Prognostic Biomarker in Hepatocellular
Guoming Chen1, Cheng Zhang1, Danyun Li2
1School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China.
Insights
HAMP gene shows promise for early hepatocellular carcinoma (HCC) diagnosis and predicting response to programmed cell death protein 1 (PD-1) immunotherapy. This discovery offers new hope for personalized HCC treatment strategies.
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Hepatocellular carcinoma (HCC) is a significant global health challenge.
- Programmed cell death protein 1 (PD-1) immunotherapy shows efficacy in various cancers but has limited sensitivity in some HCC patients.
- Identifying reliable biomarkers for HCC diagnosis and treatment response is crucial.
Purpose of the Study:
- To identify novel biomarkers for early diagnosis and predicting PD-1 immunotherapy response in HCC.
- To develop predictive models for HCC diagnosis, prognosis, and PD-1 treatment outcomes.
- To investigate the role of identified biomarkers in immune cell infiltration and immune checkpoint expression in HCC.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) datasets for HCC patients and PD-1 immunotherapy.
- Applied Lasso regression to identify key differentially expressed genes (DEGs).
- Developed prediction models using logistic regression and support vector machine (SVM) techniques.
- Validated findings using The Cancer Genome Atlas (TCGA) data.
Main Results:
- Identified HAMP and FOS as key intersecting DEGs, with HAMP demonstrating superior diagnostic and predictive capabilities for HCC and PD-1 sensitivity.
- Developed a robust SVM model using HAMP for predicting triple-classified outcomes in HCC patients undergoing PD-1 treatment.
- External validation confirmed HAMP elevation in early-stage HCC and its positive correlation with immune cell infiltration and key immune checkpoints (PDCD1, CTLA4).
Conclusions:
- HAMP serves as a novel biomarker for early HCC diagnosis, prognosis, and predicting PD-1 immunotherapy efficacy.
- Developed diagnostic, prognostic, and PD-1 treatment prediction models for HCC patients based on HAMP.
- HAMP's correlation with immune factors suggests its role in the tumor immune microenvironment and immunotherapy response.
Abstract:
Hepatocellular carcinoma (HCC) remains a global medical problem. Programmed cell death protein 1 (PD-1) is a powerful weapon against many cancers, but it is not sensitive to some patients with HCC. We obtained datasets from the Gene Expression Omnibus (GEO) database on HCC patients and PD-1 immunotherapy to select seven intersecting DEGs. Through Lasso regression, two intersecting genes were acquired as predictors of HCC and PD-1 treatment prognosis, including HAMP and FOS. Logistic regression was performed to build a prediction model. HAMP had a better ability to diagnose HCC and predict PD1 treatment sensitivity. Further, we adapted the support vector machine (SVM) technique using HAMP to predict triple-classified outcomes after PD1 treatment in HCC patients, which had an excellent classification ability. We also performed external validation using TCGA data, which showed that HAMP was elevated in the early stage of HCC. HAMP was positively correlated with the infiltration of 18 major immune cells and the expression of 2 important immune checkpoints, PDCD1 and CTLA4. We discovered a biomarker that can be used for the early diagnosis, prognosis and PD1 immunotherapy efficacy prediction of HCC for the first time and developed a diagnostic model, prognostic model and prediction model of PD1 treatment sensitivity and treatment outcome for HCC patients accordingly.
