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Updated: Aug 8, 2025
Mass Cytometry Analysis of Systemic and Local Immune Responses in Hepatocellular Carcinoma
Published on: April 25, 2025
Research into the characteristic molecules significantly affecting liver cancer immunotherapy
Junhong Chen1, Hengwei Jin1, Hao Zhou1
1Department of Hepatobiliary and Pancreatic Surgery II, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
Background:
The past decade has witnessed unprecedented scientific breakthroughs, including immunotherapy, which has great potential in clinical applications for liver cancer.
Methods:
Public data were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases and analyzed with R software.
Results:
The LASSO and SVM-RFE machine learning algorithms identified 16 differentially expressed genes (DEGs) related to immunotherapy, namely, GNG8, MYH1, CHRNA3, DPEP1, PRSS35, CKMT1B, CNKSR1, C14orf180, POU3F1, SAG, POU2AF1, IGFBPL1, CDCA7, ZNF492, ZDHHC22, and SFRP2. Moreover, a logistic model (CombinedScore) was established based on these DEGs, showing an excellent prediction performance for liver cancer immunotherapy. Patients with a low CombinedScore might respond better to immunotherapy. Gene Set Enrichment Analysis showed that many metabolism pathways were activated in patients with a high CombinedScore, including butanoate metabolism, bile acid metabolism, fatty acid metabolism, glycine serine and threonine metabolism, and propanoate metabolism. Our comprehensive analysis showed that the CombinedScore was negatively correlated with the levels of most tumor-infiltrating immune cells and the activities of key steps of cancer immunity cycles. Continually, the CombinedScore was negatively associated with the expression of most immune checkpoints and immunotherapy response-related pathways. Moreover, patients with a high and a low CombinedScore exhibited diverse genomic features. Furthermore, we found that CDCA7 was significantly correlated with patient survival. Further analysis showed that CDCA7 was positively associated with M0 macrophages and negatively associated with M2 macrophages, suggesting that CDCA7 could influence the progression of liver cancer cells by affecting macrophage polarization. Next, single-cell analysis showed that CDCA7 was mainly expressed in prolif T cells. Immunohistochemical results confirmed that the staining intensity of CDCA7 was prominently increased in the nucleus in primary liver cancer tissues compared to adjacent non-tumor tissues.
Conclusions:
Our results provide novel insights into the DEGs and factors affecting liver cancer immunotherapy. Meanwhile, CDCA7 was identified as a potential therapeutic target in this patient population.
Insights
This study identified 16 key genes and a CombinedScore model to predict liver cancer immunotherapy response. CDCA7, a potential therapeutic target, influences cancer progression by affecting macrophage polarization.
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Immunotherapy shows promise for liver cancer treatment.
- Recent scientific advancements highlight its clinical potential.
Purpose of the Study:
- To identify key genes and develop a predictive model for liver cancer immunotherapy response.
- To investigate the role of specific genes, like CDCA7, in liver cancer progression and immune cell interactions.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) public databases.
- Applied LASSO and SVM-RFE machine learning algorithms to identify differentially expressed genes (DEGs).
- Established a logistic model (CombinedScore) and performed Gene Set Enrichment Analysis and single-cell analysis.
Main Results:
- Identified 16 DEGs and developed a CombinedScore model with excellent prediction performance for liver cancer immunotherapy.
- A low CombinedScore indicated better immunotherapy response, with high scores linked to activated metabolism pathways and suppressed immune activity.
- CDCA7 expression correlated with patient survival, macrophage polarization, and T cell activity, and was upregulated in liver cancer tissues.
Conclusions:
- Novel insights into DEGs and factors influencing liver cancer immunotherapy were provided.
- CDCA7 was identified as a potential therapeutic target for liver cancer patients undergoing immunotherapy.
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