Study on the effect of glypican-3 expression on immunotherapy in liver cancer patients
10.13431/j.cnki.immunol.j.20240108
- VernacularTitle:Glypican-3表达影响临床肝癌患者免疫治疗效果的研究
- Author:
Yuxin ZHANG
1
;
Jing WANG
;
Yan XU
;
Zihe MENG
;
Penghui YANG
;
Jitao SUN
Author Information
1. 010110 呼和浩特,内蒙古医科大学基础医学院
- Publication Type:Journal Article
- Keywords:
Glypican-3;
Liver cancer;
Immunotherapy;
PD-1;
Regulatory T cells
- From:
Immunological Journal
2024;40(10):773-780
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the correlation between the expression level of glypican-3(GPC3)and the immune therapy response in clinical liver cancer patients.Methods Clinical data of 232 liver cancer immunotherapy response/tolerance group patients from January 2019 to May 2023 at the General Hospital of the People's Liberation Army were collected,and the correlation between GPC3 expression levels and the efficacy of immunotherapy in liver cancer patients was statistically analyzed;TCGA database validation of immune cell infiltration in GPC3 high and low expression groups of liver cancer patients;Further,real-time fluorescence quantitative PCR(qPCR)and immunohistochemical staining methods were used to detect the expression of GPC3 and immune cell infiltration in paired tissues of liver cancer immunotherapy response/tolerance group patients,and multi-color immunofluorescence was applied to detect the expression of GPC3 and related molecules.Results Clinical evidence shows that the GPC3 positive group of liver cancer patients has a low response rate to immunotherapy.Univariate/multivariate analysis results indicate that GPC3 is an independent risk factor for tumor recurrence after liver cancer immunotherapy;The analysis of the TCGA database revealed that high expression of GPC3 in liver cancer tissue leads to increased infiltration of regulatory T cells(Tregs);Paired tissue testing of liver cancer patients and adjacent tissues revealed that the immunotherapy effect was worse in the GPC3 high expression group,and Tregs cell infiltration increased,consistent with the results of database analysis.The TCGA database analysis results showed that GPC3 was positively correlated with CCL20 and its ligand CCR6,and the multi-color immunohistochemistry results were consistent with the database analysis results.Conclusion GPC3 is highly expressed in tumor tissues of liver cancer patients and is positively correlated with immune therapy tolerance in liver cancer.GPC3 regulates Tregs cell infiltration through the CCL20-CCR6 signaling axis and is expected to serve as a biomarker for predicting the efficacy of immune therapy in clinical liver cancer patients.
