Single-cell RNA sequencing and immune microenvironment analysis reveal PLOD2-driven malignant transformation in cervical cancer
BackgroundCervical cancer is the fourth most common cancer in women globally, and the main cause of the disease has been found to be ongoing HPV infection. Cervical cancer remains the primary cause of cancer-related death despite major improvements in screening and treatment approaches, especially i...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1522655/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841556748790398976 |
|---|---|
| author | Zhiheng Lin Fengxin Wang Renwu Yin Shengnan Li Yuquan Bai Baofang Zhang Chenlin Sui Hengjie Cao Dune Su Lianwei Xu Honghong Wang |
| author_facet | Zhiheng Lin Fengxin Wang Renwu Yin Shengnan Li Yuquan Bai Baofang Zhang Chenlin Sui Hengjie Cao Dune Su Lianwei Xu Honghong Wang |
| author_sort | Zhiheng Lin |
| collection | DOAJ |
| description | BackgroundCervical cancer is the fourth most common cancer in women globally, and the main cause of the disease has been found to be ongoing HPV infection. Cervical cancer remains the primary cause of cancer-related death despite major improvements in screening and treatment approaches, especially in low- and middle-income nations. Therefore, it is crucial to investigate the tumor microenvironment in advanced cervical cancer in order to identify possible treatment targets.Materials and methodsIn order to better understand malignant cervical cancer epithelial cells (EPCs), this study used bulk RNA-seq data from UCSC in conjunction with single-cell RNA sequencing data from the ArrayExpress database. After putting quality control procedures into place, cell type identification and clustering analysis using the Seurat software were carried out. To clarify functional pathways, enrichment analysis and differential gene expression were carried out. The CIBERSORT and ESTIMATE R packages were used to evaluate the immune microenvironment characteristics, and univariate and multivariate Cox regression analyses were used to extract prognostic features. Furthermore, assessments of drug sensitivity and functional enrichment were carried out.ResultsEight cell types were identified, with EPCs showing high proliferative and stemness features. Five EPC subpopulations were defined, with C1 NNMT+ CAEPCs driving tumor differentiation. A NNMT CAEPCs Risk Score (NCRS) model was developed, revealing a correlation between elevated NCRS scores and adverse patient outcomes characterized by immune evasion. In vitro experiments validated that the prognostic gene PLOD2 significantly enhances proliferation, migration, and invasion of cervical cancer cells.ConclusionThis investigation delineated eight cell types and five subpopulations of malignant EPCs in cervical cancer, establishing the C1 NNMT+ CAEPCs as a crucial therapeutic target. The NCRS model demonstrated its prognostic capability, indicating that higher scores are associated with poorer clinical outcomes. The validation of PLOD2 as a prognostic gene highlights its therapeutic potential, underscoring the critical need for integrating immunotherapy and targeted treatment strategies to enhance diagnostic and therapeutic approaches in cervical cancer. |
| format | Article |
| id | doaj-art-caecf9e5deb54a988368595429004c1b |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-caecf9e5deb54a988368595429004c1b2025-01-07T06:41:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15226551522655Single-cell RNA sequencing and immune microenvironment analysis reveal PLOD2-driven malignant transformation in cervical cancerZhiheng Lin0Fengxin Wang1Renwu Yin2Shengnan Li3Yuquan Bai4Baofang Zhang5Chenlin Sui6Hengjie Cao7Dune Su8Lianwei Xu9Honghong Wang10Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaThe Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Urology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaThe Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaThe Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaBackgroundCervical cancer is the fourth most common cancer in women globally, and the main cause of the disease has been found to be ongoing HPV infection. Cervical cancer remains the primary cause of cancer-related death despite major improvements in screening and treatment approaches, especially in low- and middle-income nations. Therefore, it is crucial to investigate the tumor microenvironment in advanced cervical cancer in order to identify possible treatment targets.Materials and methodsIn order to better understand malignant cervical cancer epithelial cells (EPCs), this study used bulk RNA-seq data from UCSC in conjunction with single-cell RNA sequencing data from the ArrayExpress database. After putting quality control procedures into place, cell type identification and clustering analysis using the Seurat software were carried out. To clarify functional pathways, enrichment analysis and differential gene expression were carried out. The CIBERSORT and ESTIMATE R packages were used to evaluate the immune microenvironment characteristics, and univariate and multivariate Cox regression analyses were used to extract prognostic features. Furthermore, assessments of drug sensitivity and functional enrichment were carried out.ResultsEight cell types were identified, with EPCs showing high proliferative and stemness features. Five EPC subpopulations were defined, with C1 NNMT+ CAEPCs driving tumor differentiation. A NNMT CAEPCs Risk Score (NCRS) model was developed, revealing a correlation between elevated NCRS scores and adverse patient outcomes characterized by immune evasion. In vitro experiments validated that the prognostic gene PLOD2 significantly enhances proliferation, migration, and invasion of cervical cancer cells.ConclusionThis investigation delineated eight cell types and five subpopulations of malignant EPCs in cervical cancer, establishing the C1 NNMT+ CAEPCs as a crucial therapeutic target. The NCRS model demonstrated its prognostic capability, indicating that higher scores are associated with poorer clinical outcomes. The validation of PLOD2 as a prognostic gene highlights its therapeutic potential, underscoring the critical need for integrating immunotherapy and targeted treatment strategies to enhance diagnostic and therapeutic approaches in cervical cancer.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1522655/fullcervical cancersingle-cell RNA sequencingtumor microenvironmentprognostic modelimmune evasiontherapeutic targets |
| spellingShingle | Zhiheng Lin Fengxin Wang Renwu Yin Shengnan Li Yuquan Bai Baofang Zhang Chenlin Sui Hengjie Cao Dune Su Lianwei Xu Honghong Wang Single-cell RNA sequencing and immune microenvironment analysis reveal PLOD2-driven malignant transformation in cervical cancer Frontiers in Immunology cervical cancer single-cell RNA sequencing tumor microenvironment prognostic model immune evasion therapeutic targets |
| title | Single-cell RNA sequencing and immune microenvironment analysis reveal PLOD2-driven malignant transformation in cervical cancer |
| title_full | Single-cell RNA sequencing and immune microenvironment analysis reveal PLOD2-driven malignant transformation in cervical cancer |
| title_fullStr | Single-cell RNA sequencing and immune microenvironment analysis reveal PLOD2-driven malignant transformation in cervical cancer |
| title_full_unstemmed | Single-cell RNA sequencing and immune microenvironment analysis reveal PLOD2-driven malignant transformation in cervical cancer |
| title_short | Single-cell RNA sequencing and immune microenvironment analysis reveal PLOD2-driven malignant transformation in cervical cancer |
| title_sort | single cell rna sequencing and immune microenvironment analysis reveal plod2 driven malignant transformation in cervical cancer |
| topic | cervical cancer single-cell RNA sequencing tumor microenvironment prognostic model immune evasion therapeutic targets |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1522655/full |
| work_keys_str_mv | AT zhihenglin singlecellrnasequencingandimmunemicroenvironmentanalysisrevealplod2drivenmalignanttransformationincervicalcancer AT fengxinwang singlecellrnasequencingandimmunemicroenvironmentanalysisrevealplod2drivenmalignanttransformationincervicalcancer AT renwuyin singlecellrnasequencingandimmunemicroenvironmentanalysisrevealplod2drivenmalignanttransformationincervicalcancer AT shengnanli singlecellrnasequencingandimmunemicroenvironmentanalysisrevealplod2drivenmalignanttransformationincervicalcancer AT yuquanbai singlecellrnasequencingandimmunemicroenvironmentanalysisrevealplod2drivenmalignanttransformationincervicalcancer AT baofangzhang singlecellrnasequencingandimmunemicroenvironmentanalysisrevealplod2drivenmalignanttransformationincervicalcancer AT chenlinsui singlecellrnasequencingandimmunemicroenvironmentanalysisrevealplod2drivenmalignanttransformationincervicalcancer AT hengjiecao singlecellrnasequencingandimmunemicroenvironmentanalysisrevealplod2drivenmalignanttransformationincervicalcancer AT dunesu singlecellrnasequencingandimmunemicroenvironmentanalysisrevealplod2drivenmalignanttransformationincervicalcancer AT lianweixu singlecellrnasequencingandimmunemicroenvironmentanalysisrevealplod2drivenmalignanttransformationincervicalcancer AT honghongwang singlecellrnasequencingandimmunemicroenvironmentanalysisrevealplod2drivenmalignanttransformationincervicalcancer |