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Research Highlight | June 08, 2021

New approach allows researchers to explore areas surrounding tumours to find signatures associated with prostate cancer progression

A team of researchers partly funded by the TFRI has used a novel approach to analyze tumours and the areas surrounding them, revealing a number of key signatures associated with aggressive prostate cancers.

In a paper published in Nature Cell Biology (January 2021), the team explained how they used a technique called single-cell RNA-sequencing (scRNA-seq) to analyze cancer cells and cells in the areas immediately surrounding them, also known as the tumour microenvironment (TME). This new approach allowed them to identify multiple tumour and microenvironment signatures associated with prostate cancer progression.

“Single-cell RNA-sequencing technology has created unprecedented opportunities to simultaneously assess thousands of cells within a sample, allowing us to study the heterogeneity among tumour cells and the complexity of the TME,” said Dr. Housheng Hansen He, a University Health Network researcher and a former TFRI New Investigator who was a co-senior author on the paper. “But even though this technology is increasingly being adopted by researchers, its application to prostate cancer has been limited.”

To reverse this trend, Dr. He and his team used this technology to analyze 27 prostate tissues and tumours. In total, they analyzed 111,914 individual cells, getting an in depth look of how tumour cells interact with their surrounding environment. This deep dive allowed them to find several genetic signatures associated with aggressive cancers, notably an abundance of a gene called KLK3, which may alter the ability of T-cells in TME to fight cancer cells.

“This sheds new light on how the cancer cells interact with their microenvironment to drive prostate cancer progression,” said Dr. He. “It could also help us set up tests at the time of diagnosis that search for these signatures in order to indicate which patients are more likely to progress to a more aggressive disease.”

In addition to making these significant findings, the team also set up a web-based portal for other researchers to access transcriptome data secured through scRNA-seq, creating a resource that could lead to more discoveries in the future.

Study

Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression

Authors

Sujun Chen, Guanghui Zhu, Yue Yang, Fubo Wang, Yu-Tian Xiao, Na Zhang, Xiaojie Bian, Yasheng Zhu, Yongwei Yu, Fei Liu, Keqin Dong, Javier Mariscal, Yin Liu,Fraser Soares, Helen Loo Yau, Bo Zhang, Weidong Chen, Chao Wang, Dai Chen, Qinghua Guo, Zhengfang Yi, Mingyao Liu, Michael Fraser, Daniel D. De Carvalho, Paul C. Boutros, Dolores Di Vizio, Zhou Jiang, Theodorus van der Kwast, Alejandro Berlin, Song Wu , Jianhua Wang , Housheng Hansen He and Shancheng Ren

Funding

This study was partially find by The Terry Fox New Frontiers Program Project Grant in Triggers and Targets In the Tumour Microenvironment Hypoxia and Beyond