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Updated: Aug 24, 2025
In Vitro Establishment of a Genetically Engineered Murine Head and Neck Cancer Cell Line using an Adeno-Associated Virus-Cas9 System
Published on: January 9, 2020
GPRASP1 is a candidate anti-oncogene and correlates with immune microenvironment and immunotherapeutic efficiency in
Tao Zhang1, Genglong Liu2,3, Juan Zhang1
1Department of Otolaryngology Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.
Background:
G-protein-coupled receptor-associated sorting protein 1 (GPRASP1) plays an important role in tumorigenesis. However, GPRASP1 specific role has not been clarified in head and neck cancer (HNC).
Methods:
HNC RNA sequencing (RNA-seq) datasets, DNA methylation data, somatic mutation data, copy number variation (CNV) data, and corresponding clinicopathologic information were acquired from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A comprehensive evaluation was performed to explore the relationship of GPRASP1 expression with clinicopathologic characteristics, CNV, and DNA methylation. Additionally, we employed HNC tissue microarray (TMA) to further confirm the relation between GPRASP1 expression and clinical features. Then, we systematically associated the GPRASP1 with immunological properties from numerous perspectives, such as immune cell infiltration, immune-related pathways, immune checkpoint inhibitors (ICIs), immunomodulators, immunogenicity, and immunotherapy.
Results:
Analyzing TCGA, GEO, and TMA datasets, GPRASP1 is significantly down-regulated in HNC compared to normal tissues. The expression of GPRASP1 is significantly negatively correlated with clinical features (perineural invasion, histologic grade, T stage, and TNM stage), and is an independent predictor of favorable prognosis, regardless of other clinicopathological features (HR: 0.42, 95% CI 0.20-0.91, p = 0.028). The etiological investigation found that the abnormal expression of GPRASP1 was related to DNA methylation, not CMV. Subsequently, the high expression of GPRASP1 was significantly correlated with immune cell infiltration (CD8+ T cell, tumor infiltrating lymphocyte), immune-related pathways (cytolytic activity, check-point, human leukocyte antigen), ICIs (CTLA4, HAVCR2, LAG3, PDCD1, and TIGIT), immunomodulators (CCR4/5, CXCL9, CXCR3/4/5), and immunogenicity (immune score, neoantigen, tumor mutation burden). Finally, immunophenoscore and tumor immune dysfunction and exclusion analysis demonstrated that GPRASP1 expression levels can accurately predict the immunotherapeutic response.
Conclusion:
GPRASP1 is a promising candidate biomarker that plays a role in the occurrence, development, and prognosis of HNC. Evaluating GPRASP1 expression will aid in the characterization of tumor microenvironment infiltration and orient more efficient immunotherapy strategies.
Insights
G-protein-coupled receptor-associated sorting protein 1 (GPRASP1) is down-regulated in head and neck cancer (HNC), correlating with better prognosis. High GPRASP1 expression predicts a positive response to immunotherapy by influencing the tumor immune microenvironment.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- G-protein-coupled receptor-associated sorting protein 1 (GPRASP1) is implicated in tumorigenesis.
- The specific role of GPRASP1 in head and neck cancer (HNC) remains unclear.
Purpose of the Study:
- To investigate the role of GPRASP1 in the occurrence, development, and prognosis of HNC.
- To explore the association between GPRASP1 expression and the tumor immune microenvironment in HNC.
- To evaluate GPRASP1 as a potential biomarker for predicting immunotherapy response in HNC.
Main Methods:
- Analysis of HNC RNA sequencing, DNA methylation, somatic mutation, and copy number variation data from TCGA and GEO databases.
- Correlation analysis of GPRASP1 expression with clinicopathologic features, DNA methylation, and immune properties.
- Validation using HNC tissue microarrays (TMA) and assessment of immunophenoscore and tumor immune dysfunction and exclusion.
Main Results:
- GPRASP1 is significantly down-regulated in HNC tissues and negatively correlates with advanced clinical features (perineural invasion, histologic grade, T stage, TNM stage).
- GPRASP1 is an independent predictor of favorable prognosis in HNC (HR: 0.42, 95% CI 0.20-0.91, p=0.028), with its expression linked to DNA methylation.
- High GPRASP1 expression is associated with increased immune cell infiltration (CD8+ T cells, TILs), immune-related pathways, immune checkpoint inhibitors (ICIs), immunomodulators, and immunogenicity (immune score, neoantigen, TMB), accurately predicting immunotherapy response.
Conclusions:
- GPRASP1 serves as a promising biomarker in HNC, influencing tumor occurrence, development, and prognosis.
- GPRASP1 expression levels are crucial for characterizing tumor immune microenvironment infiltration.
- Evaluating GPRASP1 can guide the development of more effective immunotherapy strategies for HNC patients.
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