RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation

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.

Automated summary

This study identified RGS1 as a core gene associated with immune status and FIGO stage in cervical cancer patients. Interaction analysis revealed significant associations between RGS1 and CD4 and RGS2. Functional enrichment analysis indicated that differentially expressed genes were related to T cell activation. High expression of RGS1 was associated with increased immune infiltration and higher expressions of immune checkpoint inhibitors (ICIs) targets. RGS1 was found to be upregulated in cervical cancer tissues, especially in HPV-E6 positive cancer tissues. Knockdown of RGS1 inhibited cell activities and promoted apoptosis in cervical cancer cell lines.