Single-Cell Proteomic Analysis Dissects the Complexity of Tumor Microenvironment in Muscle Invasive Bladder Cancer

Chao Feng; Xi Wang; Yuting Tao; Yuanliang Xie; Zhiyong Lai; Zhijian Li; Jiaxin Hu; Shaomei Tang; Lixin Pan; Liangyu He; Qiuyan Wang; Tianyu Li; Zengnan Mo

doi:10.3390/cancers13215440

Single-Cell Proteomic Analysis Dissects the Complexity of Tumor Microenvironment in Muscle Invasive Bladder Cancer

Cancers (Basel). 2021 Oct 29;13(21):5440. doi: 10.3390/cancers13215440.

Authors

Chao Feng^{1

2

3}, Xi Wang^{1

2

4}, Yuting Tao^{1

2

3}, Yuanliang Xie^{1

2

5}, Zhiyong Lai^{1

2}, Zhijian Li^{1

2}, Jiaxin Hu^{1

2}, Shaomei Tang^{1

2}, Lixin Pan^{1

2}, Liangyu He^{1

2

6

7}, Qiuyan Wang^{1

2

4}, Tianyu Li^{1

2

6

7}, Zengnan Mo^{1

2

6

7}

Affiliations

¹ Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China.
² Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning 530021, China.
³ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Guangxi Medical University, Nanning 530021, China.
⁴ Key Laboratory of Longevity and Aging-Related Diseases of Chinese Ministry of Education, Center for Translational Medicine, Guangxi Medical University, Nanning 530021, China.
⁵ Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China.
⁶ Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
⁷ Departments of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.

Abstract

Muscle invasive bladder cancer (MIBC) is a malignancy with considerable heterogeneity. The MIBC tumor microenvironment (TME) is highly complex, comprising diverse phenotypes and spatial architectures. The complexity of the MIBC TME must be characterized to provide potential targets for precision therapy. Herein, an integrated combination of mass cytometry and imaging mass cytometry was used to analyze tumor cells, immune cells, and TME spatial characteristics of 44 MIBC patients. We detected tumor and immune cell clusters with abnormal phenotypes. In particular, we identified a previously overlooked cancer stem-like cell cluster (ALDH⁺PD-L1⁺ER-β^-) that was strongly associated with poor prognosis. We elucidated the different spatial architectures of immune cells (excluded, infiltrated, and deserted) and tumor-associated collagens (curved, stretched, directionally distributed, and chaotic) in the MIBC TME. The present study is the first to provide in-depth insight into the complexity of the MIBC TME at the single-cell level. Our results will improve the general understanding of the heterogeneous characteristics of MIBC, potentially facilitating patient stratification and personalized therapy.

Keywords: cancer stem cell; imaging mass cytometry; mass cytometry; muscle invasive bladder cancer; tumor microenvironment.

Abstract

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