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RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and
Siyang Zhang1, Han Wang1, Jiao Liu1
1Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Background:
Effective treatment is needed for advanced, inoperable, or chemotherapy-resistant cervical cancer patients. Immunotherapy has become a new treatment modality for cervical cancer patients, and there is an urgent need to identify additional targets for cervical cancer immunotherapy.
Methods:
In this study the core gene, RGS1, which affects immune status and the FIGO stage of cervical cancer patients was identified by WGCNA analysis and differential analysis using TCGA database. 10 related genes interacting with RGS1 were identified using PPI network, and the functional and immune correlations were analyzed. Based on the expression of RGS1 and related genes, the consensus clustering method was used to divide CESC patients into two groups (group 1, high expression of RGS1; group 2, low expression of RGS1). Then, the functional enrichment analysis was used to search for the functional differences in differentially expressed genes (DEGs) between group 1 and group 2. Immune infiltration analysis was performed using ESTIMATE, CIBERSORT, and ssGSEA, and the differences in expression of immune checkpoint inhibitors (ICIs) targets were assessed between the two groups. We investigated the effect of RGS1 on the clinical relevance of CESC patients, and experimentally verified the differences in RGS1 expression between cervical cancer patient tissues and normal cervical tissues, the role of RGS1 in cell function, and the effect on tumor growth in tumor-bearing mice.
Results:
We found that RGS1 was associated with CD4, GNAI3, RGS2, GNAO1, GNAI2, RGS20, GNAZ, GNAI1, HLA-DRA and HLA-DRB1, especially CD4 and RGS2. Functional enrichment of DEGs was associated with T cell activation. Compared with group 2, group 1 had stronger immune infiltration and higher ICI target expression. RGS1 had higher expression in cervical cancer tissues than normal tissues, especially in HPV-E6 positive cancer tissues. In cervical cancer cell lines, knockdown of RGS1 can inhibited cell proliferation, migration, invasion, and tumor growth in nude mice and promoted apoptosis.
Conclusions:
RGS1, as an oncogenic gene of cervical cancer, affects the immune microenvironment of patients with cervical cancer and may be a target of immunotherapy.
Insights
Regulator of G protein signaling 1 (RGS1) is an oncogenic gene in cervical cancer, impacting the immune microenvironment. Targeting RGS1 may offer a new immunotherapy strategy for cervical cancer patients.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Cervical cancer, especially advanced or resistant forms, requires novel treatments.
- Immunotherapy is emerging as a treatment for cervical cancer, necessitating new therapeutic targets.
Purpose of the Study:
- To identify novel therapeutic targets for cervical cancer immunotherapy.
- To investigate the role of the core gene RGS1 in cervical cancer progression and its association with the immune microenvironment.
Main Methods:
- Weighted gene co-expression network analysis (WGCNA) and differential analysis on TCGA database to identify core genes.
- Protein-protein interaction (PPI) network analysis to identify RGS1-interacting genes.
- Consensus clustering based on RGS1 expression to stratify patients.
- Functional enrichment analysis, immune infiltration analysis (ESTIMATE, CIBERSORT, ssGSEA), and assessment of immune checkpoint inhibitor (ICI) target expression.
- Experimental validation of RGS1 expression and function in patient tissues, cell lines, and tumor xenografts.
Main Results:
- RGS1 expression is elevated in cervical cancer tissues compared to normal tissues, particularly in HPV-E6 positive cancers.
- RGS1 expression correlates with immune cell infiltration and higher expression of ICI targets.
- Knockdown of RGS1 inhibits cervical cancer cell proliferation, migration, invasion, and tumor growth in vivo, while promoting apoptosis.
- Functional enrichment analysis revealed associations with T cell activation.
Conclusions:
- RGS1 acts as an oncogenic gene in cervical cancer.
- RGS1 influences the tumor immune microenvironment in cervical cancer patients.
- RGS1 represents a potential therapeutic target for cervical cancer immunotherapy.
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