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Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer19.38 MB
Published VersionCC BY V4.0, Open Access
Journal article
Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer
Journal of Experimental and Clinical Cancer Research, Vol.42(1), pp.1-21
2023
PMID: 36683048
Abstract
Background: Cervical cancer (CC) is the 3rd most common cancer in women and the 4th 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.
Details
- Title
- Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer
- Authors
- Xiaosong Liu (Author) - First People's Hospital of FoshanGuoying Ni (Author) - University of the Sunshine Coast, Queensland, Centre for BioinnovationPingping Zhang (Author) - First People's Hospital of FoshanHejie Li (Author) - University of the Sunshine Coast, Queensland, Centre for BioinnovationJunjie Li (Author) - Guangdong Pharmaceutical UniversityBernardo Cavallazzi Sebold (Author) - University of the Sunshine Coast, Queensland, Centre for BioinnovationXiaolian Wu (Author) - First People's Hospital of FoshanGuoqiang Chen (Corresponding Author) - First People's Hospital of FoshanSonghua Yuan (Corresponding Author) - First People's Hospital of FoshanTianfang Wang (Corresponding Author) - University of the Sunshine Coast, Queensland, Centre for Bioinnovation
- Publication details
- Journal of Experimental and Clinical Cancer Research, Vol.42(1), pp.1-21
- Publisher
- BioMed Central Ltd.
- Date published
- 2023
- DOI
- 10.1186/s13046-023-02598-0
- ISSN
- 1756-9966; 0392-9078
- PMID
- 36683048
- Copyright note
- © The Author(s) 2023. Open Access This 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/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
- Grant note
- 31971355 / National Science Foundation of China 2015AG1003 / Foshan municipal Government 2019A008 / Deng Feng project of Foshan First People's Hospital 2016A020213001 / Guangdong Science and Technology Department 2020A1515010855 / National Science Foundation of Guangdong province
- Organisation Unit
- School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; GeneCology Research Centre - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99706996402621
- Output Type
- Journal article
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