Spatial transcriptomics reveals unique metabolic profile and key oncogenic regulators of cervical squamous cell carcinoma
Abstract Background As a prevalent and deadly malignant tumor, the treatment outcomes for late-stage patients with cervical squamous cell carcinoma (CSCC) are often suboptimal. Previous studies have shown that tumor progression is closely related with tumor metabolism and microenvironment reshaping,...
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BMC
2024-12-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-06011-y |
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| author | Limin Zhou Jiejie Liu Peipei Yao Xing Liu Fei Chen Yu Chen Li Zhou Chao Shen You Zhou Xin Du Junbo Hu |
| author_facet | Limin Zhou Jiejie Liu Peipei Yao Xing Liu Fei Chen Yu Chen Li Zhou Chao Shen You Zhou Xin Du Junbo Hu |
| author_sort | Limin Zhou |
| collection | DOAJ |
| description | Abstract Background As a prevalent and deadly malignant tumor, the treatment outcomes for late-stage patients with cervical squamous cell carcinoma (CSCC) are often suboptimal. Previous studies have shown that tumor progression is closely related with tumor metabolism and microenvironment reshaping, with disruptions in energy metabolism playing a critical role in this process. To delve deeper into the understanding of CSCC development, our research focused on analyzing the tumor microenvironment and metabolic characteristics across different regions of tumor tissue. Methods Utilizing spatial transcriptomics (ST) sequencing technology, we conducted a study on FFPE (formalin-fixed paraffin-embedded) tumor samples from CSCC patients. Coupled with single-cell RNA sequencing (scRNA-seq) data after deconvolution, we described spatial distribution maps of tumor leading edge and core regions in detail. Tumor tissues were classified into hypermetabolic and hypometabolic regions to analyze the metabolism profiles and tumor differentiation degree across different spatial areas. We also employed The Cancer Genome Atlas (TCGA) database to examine the analysis results of ST data. Results Our findings indicated a more complex tumor microenvironment in hypermetabolic regions. Cell-cell communication analysis showed that various cells in tumor microenvironment were influenced by the signalling molecule APP released by cancer cells and higher expression of APP was observed in hypermetabolic regions. Furthermore, our results revealed the correlation between APP and the transcription factor TRPS1. Both APP and TRPS1 demonstrated significant effects on cancer cell proliferation, migration, and invasion, potentially contributing to tumor progression. Conclusions Utilizing ST, scRNA-seq, and TCGA database, we examined the spatial metabolic profiles of CSCC tissues, including metabolism distribution, metabolic variations, and the relationship between metabolism and tumor differentiation degree. Additionally, potential cancer-promoting factors were proposed, offering a valuable foundation for the development of more effective treatment strategies for CSCC. |
| format | Article |
| id | doaj-art-ca5fe8024c3a4434a1dfaaa91b4d8a42 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-ca5fe8024c3a4434a1dfaaa91b4d8a422025-01-05T12:44:29ZengBMCJournal of Translational Medicine1479-58762024-12-0122112110.1186/s12967-024-06011-ySpatial transcriptomics reveals unique metabolic profile and key oncogenic regulators of cervical squamous cell carcinomaLimin Zhou0Jiejie Liu1Peipei Yao2Xing Liu3Fei Chen4Yu Chen5Li Zhou6Chao Shen7You Zhou8Xin Du9Junbo Hu10Tongji Medical College, Maternal and Child Health Hospital of Hubei Province, Huazhong University of Science and TechnologyState Key Laboratory of Virology, College of Life Sciences and Frontier Science Center for Immunology and Metabolism, RNA Institute, Wuhan UniversityAnimal Bio-Safety Level III Laboratory/Institute for Vaccine Research, Taikang Medical School (School of Basic Medical Sciences), Wuhan UniversityState Key Laboratory of Virology, College of Life Sciences and Frontier Science Center for Immunology and Metabolism, RNA Institute, Wuhan UniversityAnimal Bio-Safety Level III Laboratory/Institute for Vaccine Research, Taikang Medical School (School of Basic Medical Sciences), Wuhan UniversityState Key Laboratory of Virology, College of Life Sciences and Frontier Science Center for Immunology and Metabolism, RNA Institute, Wuhan UniversityAnimal Bio-Safety Level III Laboratory/Institute for Vaccine Research, Taikang Medical School (School of Basic Medical Sciences), Wuhan UniversityHubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan UniversitySystems Immunity Research Institute, Cardiff UniversityTongji Medical College, Maternal and Child Health Hospital of Hubei Province, Huazhong University of Science and TechnologyTongji Medical College, Maternal and Child Health Hospital of Hubei Province, Huazhong University of Science and TechnologyAbstract Background As a prevalent and deadly malignant tumor, the treatment outcomes for late-stage patients with cervical squamous cell carcinoma (CSCC) are often suboptimal. Previous studies have shown that tumor progression is closely related with tumor metabolism and microenvironment reshaping, with disruptions in energy metabolism playing a critical role in this process. To delve deeper into the understanding of CSCC development, our research focused on analyzing the tumor microenvironment and metabolic characteristics across different regions of tumor tissue. Methods Utilizing spatial transcriptomics (ST) sequencing technology, we conducted a study on FFPE (formalin-fixed paraffin-embedded) tumor samples from CSCC patients. Coupled with single-cell RNA sequencing (scRNA-seq) data after deconvolution, we described spatial distribution maps of tumor leading edge and core regions in detail. Tumor tissues were classified into hypermetabolic and hypometabolic regions to analyze the metabolism profiles and tumor differentiation degree across different spatial areas. We also employed The Cancer Genome Atlas (TCGA) database to examine the analysis results of ST data. Results Our findings indicated a more complex tumor microenvironment in hypermetabolic regions. Cell-cell communication analysis showed that various cells in tumor microenvironment were influenced by the signalling molecule APP released by cancer cells and higher expression of APP was observed in hypermetabolic regions. Furthermore, our results revealed the correlation between APP and the transcription factor TRPS1. Both APP and TRPS1 demonstrated significant effects on cancer cell proliferation, migration, and invasion, potentially contributing to tumor progression. Conclusions Utilizing ST, scRNA-seq, and TCGA database, we examined the spatial metabolic profiles of CSCC tissues, including metabolism distribution, metabolic variations, and the relationship between metabolism and tumor differentiation degree. Additionally, potential cancer-promoting factors were proposed, offering a valuable foundation for the development of more effective treatment strategies for CSCC.https://doi.org/10.1186/s12967-024-06011-yCervical squamous cell carcinoma (CSCC)Spatial transcriptomics (ST)APPTRPS1Tumor metabolism |
| spellingShingle | Limin Zhou Jiejie Liu Peipei Yao Xing Liu Fei Chen Yu Chen Li Zhou Chao Shen You Zhou Xin Du Junbo Hu Spatial transcriptomics reveals unique metabolic profile and key oncogenic regulators of cervical squamous cell carcinoma Journal of Translational Medicine Cervical squamous cell carcinoma (CSCC) Spatial transcriptomics (ST) APP TRPS1 Tumor metabolism |
| title | Spatial transcriptomics reveals unique metabolic profile and key oncogenic regulators of cervical squamous cell carcinoma |
| title_full | Spatial transcriptomics reveals unique metabolic profile and key oncogenic regulators of cervical squamous cell carcinoma |
| title_fullStr | Spatial transcriptomics reveals unique metabolic profile and key oncogenic regulators of cervical squamous cell carcinoma |
| title_full_unstemmed | Spatial transcriptomics reveals unique metabolic profile and key oncogenic regulators of cervical squamous cell carcinoma |
| title_short | Spatial transcriptomics reveals unique metabolic profile and key oncogenic regulators of cervical squamous cell carcinoma |
| title_sort | spatial transcriptomics reveals unique metabolic profile and key oncogenic regulators of cervical squamous cell carcinoma |
| topic | Cervical squamous cell carcinoma (CSCC) Spatial transcriptomics (ST) APP TRPS1 Tumor metabolism |
| url | https://doi.org/10.1186/s12967-024-06011-y |
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