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

Molecular Cancer

Xinghua Pan¹  Zunfu Ke²  Zhe-Sheng Chen³  Zhangang Xiao⁴  Yongjian Yue⁵  Fengyan Hu⁵  Shaowei Dong⁵  Dale Liu⁵  Lipeng Chen⁵  Kaisheng Liu⁵  Qiaoyun Long⁵  Xiaoshi Ma⁵  Jinquan Xia⁵  Kefeng Xiao⁵  Zhiqiang Cheng⁶  Jinan Guo⁶  Pan Zhao⁶  Chang Zou⁷ 

[1] Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China;Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, Guangdong, China;Guangdong-Hongkong-Macao Great Bar Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, Guangdong, China;Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China;Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, New York, USA;Key Laboratory of Medical Electrophysiology of Education Ministry, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China;Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China;Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China;Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis, Shenzhen, Guangdong, China;Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China;Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis, Shenzhen, Guangdong, China;Key Laboratory of Medical Electrophysiology of Education Ministry, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China;

关键词: Prostate cancer;    Single-cell RNA sequencing;    Diagnosis and stratification biomarker;    HPN;   

DOI  :  10.1186/s12943-020-01264-9

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsCell 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.ResultsFifteen 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.ConclusionOur findings provide a valuable resource for interpreting tumor heterogeneity in prostate cancer, and a novel candidate marker for prostate cancer management.

【 授权许可】

CC BY