Single-Cell RNA-seq Reveals The Cellular Ecosystem of Prostate Cancer

Posted by Vivian creative on May 4th, 2022

Cancer occurs once cells in any part of the body begin to grow out of control and these cancer cells can spread to other areas of the body. Prostate cancer begins when cells in the prostate, a gland only found in males, start to uncontrollably grow and has become one of the most commonly diagnosed cancers (just after skin cancer) among men, causing a few millions of deaths per year globally. It\'s noticed that advanced or metastatic prostate cancer is increasingly diagnosed, while tumors have heterogeneous cell collections with distinct genetic and phenotypic properties, meaning they can promote progression and metastasis of cancer as well as drug resistance in different ways. Thus, it\'s urgently called for further understanding of prostate cancer heterogeneity and improvement in treatment strategies.

About Intra-tumoral Heterogeneity

The complex nature of prostate cancer contributes to the accumulation of mutations, resulting in the increase of genetic diversity and the acquisition of distinct tumor subclones. Tumor heterogeneity could be caused by both genetic and non-genetic mechanisms. Cancer cells are hierarchically organized with a stem cell-like population, which sustains tumor growth by self-renewal and differentiation. On the other hand, the tumor microenvironment also generates intra-tumoral heterogeneity by applying different selective pressures in different regions of the tumor. All these mechanisms act together to create a complex system that has multiple layers of heterogeneity led by different genetic, transcriptomic, and functional properties of different cells.

As a result, it\'s necessary and important to understand the function and effect of different cell populations on tumorigenesis. Emerging single-cell omics for prostate cancer offers a chance to profile different cells within tumors and investigate what functions they perform in these processes. It\'s assumed that different tumor subclones can acquire transcriptional changes to coordinate the survival, growth, and competition of subclones in the tumor evolution process. Using single-cell RNA sequencing (scRNA-seq) technology allows researchers to evaluate tumor cell transcriptional status among different tumor subclones in untreated prostate cancer patients.

In a recently published study, researchers performed single-cell RNA sequencing of primary tumor tissues from 14 untreated patients with prostate cancer and profiling of the tumor microenvironment, and then they observed a large degree of intra-tumoral genomic and transcriptional heterogeneity when analyzing these data. Subclones within a patient displayed the unique plasticity of cell differentiation states as well as their communication patterns with other cell types within the prostate cancer ecosystem, implicating both tumor composition analysis for diagnostics and therapeutic assignment.

Characteristically, this research indicated that different subclones within a single primary tumor show different combinations of preferential subtypes. Besides, subclones showed different communication strengths with other cell types within the tumor ecosystem, which may affect the distinct transcriptional subtypes of the subclones. Moreover, researchers also discovered that both tumor cell transcriptional heterogeneity and cellular ecosystem diversity are related to features of a poor prognosis of prostate cancer. Therefore, this study using single-cell RNA-seq revealed the developmental hierarch and subclonal evolution in the cellular ecosystem of prostate cancer, providing implications for patient prognosis.

About the Author

Vivian is an expert in single-cell RNA sequencing, especially in single-cell omics for prostate cancer.