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Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer

BACKGROUND: Cervical cancer (CC) is the 3(rd) most common cancer in women and the 4(th) leading cause of deaths in gynaecological malignancies, yet the exact progression of CC is inconclusive, mainly due to the high complexity of the changing tumour microenvironment (TME) at different stages of tumo...

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Autores principales: Liu, Xiaosong, Ni, Guoying, Zhang, Pingping, Li, Hejie, Li, Junjie, Cavallazzi Sebold, Bernardo, Wu, Xiaolian, Chen, Guoqiang, Yuan, Songhua, Wang, Tianfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869594/
https://www.ncbi.nlm.nih.gov/pubmed/36683048
http://dx.doi.org/10.1186/s13046-023-02598-0
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author Liu, Xiaosong
Ni, Guoying
Zhang, Pingping
Li, Hejie
Li, Junjie
Cavallazzi Sebold, Bernardo
Wu, Xiaolian
Chen, Guoqiang
Yuan, Songhua
Wang, Tianfang
author_facet Liu, Xiaosong
Ni, Guoying
Zhang, Pingping
Li, Hejie
Li, Junjie
Cavallazzi Sebold, Bernardo
Wu, Xiaolian
Chen, Guoqiang
Yuan, Songhua
Wang, Tianfang
author_sort Liu, Xiaosong
collection PubMed
description BACKGROUND: Cervical cancer (CC) is the 3(rd) most common cancer in women and the 4(th) leading cause of deaths in gynaecological malignancies, yet the exact progression of CC is inconclusive, mainly due to the high complexity of the changing tumour microenvironment (TME) at different stages of tumorigenesis. Importantly, a detailed comparative single-nucleus transcriptomic analysis of tumour microenvironment (TME) of CC patients at different stages is lacking. METHODS: In this study, a total of 42,928 and 29,200 nuclei isolated from the tumour tissues of stage-I and II CC patients and subjected to single-nucleus RNA sequencing (snRNA-seq) analysis. The cell heterogeneity and functions were comparatively investigated using bioinformatic tools. In addition, label-free quantitative mass spectrometry based proteomic analysis was carried out. The proteome profiles of stage-I and II CC patients were compared, and an integrative analysis with the snRNA-seq was performed. RESULTS: Compared with the stage-I CC (CCI) patients, the immune response relevant signalling pathways were largely suppressed in various immune cells of the stage-II CC (CCII) patients, yet the signalling associated with cell and tissue development was enriched, as well as metabolism for energy production suggested by the upregulation of genes associated with mitochondria. This was consistent with the quantitative proteomic analysis that showed the dominance of proteins promoting cell growth and intercellular matrix development in the TME of CCII group. The interferon-α and γ responses appeared the most activated pathways in many cell populations of the CCI patients. Several collagens, such as COL12A1, COL5A1, COL4A1 and COL4A2, were found significantly upregulated in the CCII group, suggesting their roles in diagnosing CC progression. A novel transcript AC244205.1 was detected as the most upregulated gene in CCII patients, and its possible mechanistic role in CC may be investigated further. CONCLUSIONS: Our study provides important resources for decoding the progression of CC and set the foundation for developing novel approaches for diagnosing CC and tackling the immunosuppressive TME. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-023-02598-0.
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spelling pubmed-98695942023-01-24 Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer Liu, Xiaosong Ni, Guoying Zhang, Pingping Li, Hejie Li, Junjie Cavallazzi Sebold, Bernardo Wu, Xiaolian Chen, Guoqiang Yuan, Songhua Wang, Tianfang J Exp Clin Cancer Res Research BACKGROUND: Cervical cancer (CC) is the 3(rd) most common cancer in women and the 4(th) leading cause of deaths in gynaecological malignancies, yet the exact progression of CC is inconclusive, mainly due to the high complexity of the changing tumour microenvironment (TME) at different stages of tumorigenesis. Importantly, a detailed comparative single-nucleus transcriptomic analysis of tumour microenvironment (TME) of CC patients at different stages is lacking. METHODS: In this study, a total of 42,928 and 29,200 nuclei isolated from the tumour tissues of stage-I and II CC patients and subjected to single-nucleus RNA sequencing (snRNA-seq) analysis. The cell heterogeneity and functions were comparatively investigated using bioinformatic tools. In addition, label-free quantitative mass spectrometry based proteomic analysis was carried out. The proteome profiles of stage-I and II CC patients were compared, and an integrative analysis with the snRNA-seq was performed. RESULTS: Compared with the stage-I CC (CCI) patients, the immune response relevant signalling pathways were largely suppressed in various immune cells of the stage-II CC (CCII) patients, yet the signalling associated with cell and tissue development was enriched, as well as metabolism for energy production suggested by the upregulation of genes associated with mitochondria. This was consistent with the quantitative proteomic analysis that showed the dominance of proteins promoting cell growth and intercellular matrix development in the TME of CCII group. The interferon-α and γ responses appeared the most activated pathways in many cell populations of the CCI patients. Several collagens, such as COL12A1, COL5A1, COL4A1 and COL4A2, were found significantly upregulated in the CCII group, suggesting their roles in diagnosing CC progression. A novel transcript AC244205.1 was detected as the most upregulated gene in CCII patients, and its possible mechanistic role in CC may be investigated further. CONCLUSIONS: Our study provides important resources for decoding the progression of CC and set the foundation for developing novel approaches for diagnosing CC and tackling the immunosuppressive TME. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-023-02598-0. BioMed Central 2023-01-23 /pmc/articles/PMC9869594/ /pubmed/36683048 http://dx.doi.org/10.1186/s13046-023-02598-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Xiaosong
Ni, Guoying
Zhang, Pingping
Li, Hejie
Li, Junjie
Cavallazzi Sebold, Bernardo
Wu, Xiaolian
Chen, Guoqiang
Yuan, Songhua
Wang, Tianfang
Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer
title Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer
title_full Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer
title_fullStr Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer
title_full_unstemmed Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer
title_short Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer
title_sort single-nucleus rna sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-i and ii cervical cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869594/
https://www.ncbi.nlm.nih.gov/pubmed/36683048
http://dx.doi.org/10.1186/s13046-023-02598-0
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