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Molecular Cancer
Published in: Molecular Cancer 1/2020

01-12-2020 | Prostate Cancer | Research

Identification of a distinct luminal subgroup diagnosing and stratifying early stage prostate cancer by tissue-based single-cell RNA sequencing

Authors: Xiaoshi Ma, Jinan Guo, Kaisheng Liu, Lipeng Chen, Dale Liu, Shaowei Dong, Jinquan Xia, Qiaoyun Long, Yongjian Yue, Pan Zhao, Fengyan Hu, Zhangang Xiao, Xinghua Pan, Kefeng Xiao, Zhiqiang Cheng, Zunfu Ke, Zhe-Sheng Chen, Chang Zou

Published in: Molecular Cancer | Issue 1/2020

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Abstract

Background

The highly intra-tumoral heterogeneity and complex cell origination of prostate cancer greatly limits the utility of traditional bulk RNA sequencing in finding better biomarker for disease diagnosis and stratification. Tissue specimens based single-cell RNA sequencing holds great promise for identification of novel biomarkers. However, this technique has yet been used in the study of prostate cancer heterogeneity.

Methods

Cell types and the corresponding marker genes were identified by single-cell RNA sequencing. Malignant states of different clusters were evaluated by copy number variation analysis and differentially expressed genes of pseudo-bulks sequencing. Diagnosis and stratification of prostate cancer was estimated by receiver operating characteristic curves of marker genes. Expression characteristics of marker genes were verified by immunostaining.

Results

Fifteen cell groups including three luminal clusters with different expression profiles were identified in prostate cancer tissues. The luminal cluster with the highest copy number variation level and marker genes enriched in prostate cancer-related metabolic processes was considered the malignant cluster. This cluster contained a distinct subgroup with high expression level of prostate cancer biomarkers and a strong distinguishing ability of normal and cancerous prostates across different pathology grading. In addition, we identified another marker gene, Hepsin (HPN), with a 0.930 area under the curve score distinguishing normal tissue from prostate cancer lesion. This finding was further validated by immunostaining of HPN in prostate cancer tissue array.

Conclusion

Our findings provide a valuable resource for interpreting tumor heterogeneity in prostate cancer, and a novel candidate marker for prostate cancer management.
Appendix
Available only for authorised users
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Metadata
Title
Identification of a distinct luminal subgroup diagnosing and stratifying early stage prostate cancer by tissue-based single-cell RNA sequencing
Authors
Xiaoshi Ma
Jinan Guo
Kaisheng Liu
Lipeng Chen
Dale Liu
Shaowei Dong
Jinquan Xia
Qiaoyun Long
Yongjian Yue
Pan Zhao
Fengyan Hu
Zhangang Xiao
Xinghua Pan
Kefeng Xiao
Zhiqiang Cheng
Zunfu Ke
Zhe-Sheng Chen
Chang Zou
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2020
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-020-01264-9

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