RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation
Abstract 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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03526-0 |
| _version_ | 1811222406809780224 |
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| author | Siyang Zhang Han Wang Jiao Liu Tao Tao Zhi Zeng Min Wang |
| author_facet | Siyang Zhang Han Wang Jiao Liu Tao Tao Zhi Zeng Min Wang |
| author_sort | Siyang Zhang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-12T08:15:22Z |
| format | Article |
| id | doaj.art-2303811398e94fd49c3b72101bbc4091 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-12T08:15:22Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-2303811398e94fd49c3b72101bbc40912022-12-22T03:40:48ZengBMCJournal of Translational Medicine1479-58762022-07-0120111710.1186/s12967-022-03526-0RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validationSiyang Zhang0Han Wang1Jiao Liu2Tao Tao3Zhi Zeng4Min Wang5Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical UniversityDepartment of Obstetrics and Gynecology, Shengjing Hospital of China Medical UniversityDepartment of Obstetrics and Gynecology, Shengjing Hospital of China Medical UniversityDepartment of Obstetrics and Gynecology, Shengjing Hospital of China Medical UniversityDepartment of Obstetrics and Gynecology, Shengjing Hospital of China Medical UniversityDepartment of Obstetrics and Gynecology, Shengjing Hospital of China Medical UniversityAbstract 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.https://doi.org/10.1186/s12967-022-03526-0Cervical cancerImmune checkpoint inhibitorsComputational biologyImmune infiltration |
| spellingShingle | Siyang Zhang Han Wang Jiao Liu Tao Tao Zhi Zeng Min Wang RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation Journal of Translational Medicine Cervical cancer Immune checkpoint inhibitors Computational biology Immune infiltration |
| title | RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation |
| title_full | RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation |
| title_fullStr | RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation |
| title_full_unstemmed | RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation |
| title_short | RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation |
| title_sort | rgs1 and related genes as potential targets for immunotherapy in cervical cancer computational biology and experimental validation |
| topic | Cervical cancer Immune checkpoint inhibitors Computational biology Immune infiltration |
| url | https://doi.org/10.1186/s12967-022-03526-0 |
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