Characterizing tumor biology and immune microenvironment in high-grade serous ovarian cancer via single-cell RNA sequencing: insights for targeted and personalized immunotherapy strategies
BackgroundHigh-grade serous ovarian cancer (HGSOC), the predominant subtype of epithelial ovarian cancer, is frequently diagnosed at an advanced stage due to its nonspecific early symptoms. Despite standard treatments, including cytoreductive surgery and platinum-based chemotherapy, significant impr...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500153/full |
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| author | Fu Zhao Fu Zhao Xiaojing Jiang Yumeng Li Tianjiao Huang Zhikai Xiahou Wenyang Nie Qian Li |
| author_facet | Fu Zhao Fu Zhao Xiaojing Jiang Yumeng Li Tianjiao Huang Zhikai Xiahou Wenyang Nie Qian Li |
| author_sort | Fu Zhao |
| collection | DOAJ |
| description | BackgroundHigh-grade serous ovarian cancer (HGSOC), the predominant subtype of epithelial ovarian cancer, is frequently diagnosed at an advanced stage due to its nonspecific early symptoms. Despite standard treatments, including cytoreductive surgery and platinum-based chemotherapy, significant improvements in survival have been limited. Understanding the molecular mechanisms, immune landscape, and drug sensitivity of HGSOC is crucial for developing more effective and personalized therapies. This study integrates insights from cancer immunology, molecular profiling, and drug sensitivity analysis to identify novel therapeutic targets and improve treatment outcomes. Utilizing single-cell RNA sequencing (scRNA-seq), the study systematically examines tumor heterogeneity and immune microenvironment, focusing on biomarkers influencing drug response and immune activity, aiming to enhance patient outcomes and quality of life.MethodsscRNA-seq data was obtained from the GEO database in this study. Differential gene expression was analyzed using gene ontology and gene set enrichment methods. InferCNV identified malignant epithelial cells, while Monocle, Cytotrace, and Slingshot software inferred subtype differentiation trajectories. The CellChat software package predicted cellular communication between malignant cell subtypes and other cells, while pySCENIC analysis was utilized to identify transcription factor regulatory networks within malignant cell subtypes. Finally, the analysis results were validated through functional experiments, and a prognostic model was developed to assess prognosis, immune infiltration, and drug sensitivity across various risk groups.ResultsThis study investigated the cellular heterogeneity of HGSOC using scRNA-seq, focusing on tumor cell subtypes and their interactions within the tumor microenvironment. We confirmed the key role of the C2 IGF2+ tumor cell subtype in HGSOC, which was significantly associated with poor prognosis and high levels of chromosomal copy number variations. This subtype was located at the terminal differentiation of the tumor, displaying a higher degree of malignancy and close association with stage IIIC tissue types. The C2 subtype was also associated with various metabolic pathways, such as glycolysis and riboflavin metabolism, as well as programmed cell death processes. The study highlighted the complex interactions between the C2 subtype and fibroblasts through the MK signaling pathway, which may be closely related to tumor-associated fibroblasts and tumor progression. Elevated expression of PRRX1 was significantly connected to the C2 subtype and may impact disease progression by modulating gene transcription. A prognostic model based on the C2 subtype demonstrated its association with adverse prognosis outcomes, emphasizing the importance of immune infiltration and drug sensitivity analysis in clinical intervention strategies.ConclusionThis study integrates molecular oncology, immunotherapy, and drug sensitivity analysis to reveal the mechanisms driving HGSOC progression and treatment resistance. The C2 IGF2+ tumor subtype, linked to poor prognosis, offers a promising target for future therapies. Emphasizing immune infiltration and drug sensitivity, the research highlights personalized strategies to improve survival and quality of life for HGSOC patients. |
| format | Article |
| id | doaj-art-797299ef07a744769ad1a1bfecfe7c5a |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-797299ef07a744769ad1a1bfecfe7c5a2025-01-17T06:51:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15001531500153Characterizing tumor biology and immune microenvironment in high-grade serous ovarian cancer via single-cell RNA sequencing: insights for targeted and personalized immunotherapy strategiesFu Zhao0Fu Zhao1Xiaojing Jiang2Yumeng Li3Tianjiao Huang4Zhikai Xiahou5Wenyang Nie6Qian Li7Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, ChinaShandong University of Traditional Chinese Medicine, Jinan, ChinaAffiliated Hospital of Shandong Academy of Traditional Chinese Medicine, Jinan, ChinaShandong University of Traditional Chinese Medicine, Jinan, ChinaThe First School of Clinical Medicine, Heilongjiang University of Traditional Chinese Medicine, Harbin, ChinaChina Institute of Sport and Health Science, Beijing Sport University, Beijing, ChinaShandong University of Traditional Chinese Medicine, Jinan, ChinaXiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, ChinaBackgroundHigh-grade serous ovarian cancer (HGSOC), the predominant subtype of epithelial ovarian cancer, is frequently diagnosed at an advanced stage due to its nonspecific early symptoms. Despite standard treatments, including cytoreductive surgery and platinum-based chemotherapy, significant improvements in survival have been limited. Understanding the molecular mechanisms, immune landscape, and drug sensitivity of HGSOC is crucial for developing more effective and personalized therapies. This study integrates insights from cancer immunology, molecular profiling, and drug sensitivity analysis to identify novel therapeutic targets and improve treatment outcomes. Utilizing single-cell RNA sequencing (scRNA-seq), the study systematically examines tumor heterogeneity and immune microenvironment, focusing on biomarkers influencing drug response and immune activity, aiming to enhance patient outcomes and quality of life.MethodsscRNA-seq data was obtained from the GEO database in this study. Differential gene expression was analyzed using gene ontology and gene set enrichment methods. InferCNV identified malignant epithelial cells, while Monocle, Cytotrace, and Slingshot software inferred subtype differentiation trajectories. The CellChat software package predicted cellular communication between malignant cell subtypes and other cells, while pySCENIC analysis was utilized to identify transcription factor regulatory networks within malignant cell subtypes. Finally, the analysis results were validated through functional experiments, and a prognostic model was developed to assess prognosis, immune infiltration, and drug sensitivity across various risk groups.ResultsThis study investigated the cellular heterogeneity of HGSOC using scRNA-seq, focusing on tumor cell subtypes and their interactions within the tumor microenvironment. We confirmed the key role of the C2 IGF2+ tumor cell subtype in HGSOC, which was significantly associated with poor prognosis and high levels of chromosomal copy number variations. This subtype was located at the terminal differentiation of the tumor, displaying a higher degree of malignancy and close association with stage IIIC tissue types. The C2 subtype was also associated with various metabolic pathways, such as glycolysis and riboflavin metabolism, as well as programmed cell death processes. The study highlighted the complex interactions between the C2 subtype and fibroblasts through the MK signaling pathway, which may be closely related to tumor-associated fibroblasts and tumor progression. Elevated expression of PRRX1 was significantly connected to the C2 subtype and may impact disease progression by modulating gene transcription. A prognostic model based on the C2 subtype demonstrated its association with adverse prognosis outcomes, emphasizing the importance of immune infiltration and drug sensitivity analysis in clinical intervention strategies.ConclusionThis study integrates molecular oncology, immunotherapy, and drug sensitivity analysis to reveal the mechanisms driving HGSOC progression and treatment resistance. The C2 IGF2+ tumor subtype, linked to poor prognosis, offers a promising target for future therapies. Emphasizing immune infiltration and drug sensitivity, the research highlights personalized strategies to improve survival and quality of life for HGSOC patients.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500153/fullhigh-grade serous ovarian cancer (HGSOC)prognostic modelimmunotherapymolecular mechanismstumor microenvironmentmulti-omics |
| spellingShingle | Fu Zhao Fu Zhao Xiaojing Jiang Yumeng Li Tianjiao Huang Zhikai Xiahou Wenyang Nie Qian Li Characterizing tumor biology and immune microenvironment in high-grade serous ovarian cancer via single-cell RNA sequencing: insights for targeted and personalized immunotherapy strategies Frontiers in Immunology high-grade serous ovarian cancer (HGSOC) prognostic model immunotherapy molecular mechanisms tumor microenvironment multi-omics |
| title | Characterizing tumor biology and immune microenvironment in high-grade serous ovarian cancer via single-cell RNA sequencing: insights for targeted and personalized immunotherapy strategies |
| title_full | Characterizing tumor biology and immune microenvironment in high-grade serous ovarian cancer via single-cell RNA sequencing: insights for targeted and personalized immunotherapy strategies |
| title_fullStr | Characterizing tumor biology and immune microenvironment in high-grade serous ovarian cancer via single-cell RNA sequencing: insights for targeted and personalized immunotherapy strategies |
| title_full_unstemmed | Characterizing tumor biology and immune microenvironment in high-grade serous ovarian cancer via single-cell RNA sequencing: insights for targeted and personalized immunotherapy strategies |
| title_short | Characterizing tumor biology and immune microenvironment in high-grade serous ovarian cancer via single-cell RNA sequencing: insights for targeted and personalized immunotherapy strategies |
| title_sort | characterizing tumor biology and immune microenvironment in high grade serous ovarian cancer via single cell rna sequencing insights for targeted and personalized immunotherapy strategies |
| topic | high-grade serous ovarian cancer (HGSOC) prognostic model immunotherapy molecular mechanisms tumor microenvironment multi-omics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500153/full |
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