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

Journal of Experimental & Clinical Cancer Research

Research

Pingping Zhang¹  Xiaolian Wu¹  Guoqiang Chen¹  Xiaosong Liu²  Guoying Ni³  Bernardo Cavallazzi Sebold⁴  Tianfang Wang⁴  Hejie Li⁵  Songhua Yuan⁶  Junjie Li⁷ 

[1] Cancer Research Institute, First People’s Hospital of Foshan, 528000, Foshan, Guangdong, China;Cancer Research Institute, First People’s Hospital of Foshan, 528000, Foshan, Guangdong, China;The First Affiliated Hospital/School of Clinical Medicineof, Guangdong Pharmaceutical University, 510080, Guangzhou, Guangdong, China;Cancer Research Institute, First People’s Hospital of Foshan, 528000, Foshan, Guangdong, China;The First Affiliated Hospital/School of Clinical Medicineof, Guangdong Pharmaceutical University, 510080, Guangzhou, Guangdong, China;Centre for Bioinnovation, University of the Sunshine Coast, 4558, Maroochydore BC, QLD, Australia;Centre for Bioinnovation, University of the Sunshine Coast, 4558, Maroochydore BC, QLD, Australia;Centre for Bioinnovation, University of the Sunshine Coast, 4558, Maroochydore BC, QLD, Australia;School of Science, Technology and Engineering, University of the Sunshine Coast, 4558, Maroochydore BC, QLD, Australia;Department of Gynaecology, First People’s Hospital of Foshan, 528000, Foshan, Guangdong, China;The First Affiliated Hospital/School of Clinical Medicineof, Guangdong Pharmaceutical University, 510080, Guangzhou, Guangdong, China;

关键词: Single-nucleus RNA sequencing;    Quantitative proteomics;    Tumour microenvironment;    Cervical cancer;    Macrophage;    Collagen;   

DOI  :  10.1186/s13046-023-02598-0

 received in 2022-10-05, accepted in 2023-01-10,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCervical 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.MethodsIn 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.ResultsCompared 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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