The Promise of Single-cell Omics for Prostate Cancer

Posted by Vivian creative on August 4th, 2021

Prostate cancer is one of the most common malignancies for men. Most of the time, patients are unaware of this disease as prostate cancer may appear with no signs or symptoms at the early stage. However, cancer gets advanced with the occurrence of uncomfortable signs and symptoms like trouble urinating, decreased force in the stream of urine, blood in the urine, blood in the semen, bone pain, abnormal weight loss, urinary incontinence, and erectile dysfunction. It grows relatively slow in most cases and is confined to the prostate gland, while some other types of prostate cancer are aggressive to spread quickly to other tissues.

Though the causes for prostate cancer are not fully understood, studies show that the complicated interactions between tumor cells and surrounding epithelial as well as stromal cells contribute to the development of prostate cancer. It suggests that prostate epithelial cells may transition from cellular state to carcinogenesis.

Hardly can researchers understood the cellular heterogeneity in the tumor microenvironment based on previous prostate cancer studies of bulk tissue and tumor measurement, leaving many key issues unaddressed. Fortunately, molecular biology made great progress through genome-wide and whole-transcriptome sequencing studies in individual cells, enabling researchers to look into DNA, RNA, protein, and chromatin at a single-cell level with the aid of cell separation and next-generation sequencing (NGS).

The combination study of single-cell genomics, epigenomics, transcriptomics, and proteomics provides a clear overview of the variability between cells, unveiling the differences between gene and protein expression in cells, even in the same tissue with identical genes. Thus, single-cell omics for prostate cancer samples are likely to help understand the evolution and diversity of cancer, cellular composition, and intercellular interactions.

Single-cell sequencing (SCS) is one of the powerful single-cell omics strategies for immunity and microbiome, widely used in oncology, microbiology, neuroscience, botany, and other life science research. In a study of cellular state heterogeneity in human localized prostate cancer, scientists applied the single-cell RNA-sequencing (scRNA-seq) on prostate biopsies, radical prostatectomy specimens, and matched patient-derived organoids from localized prostate cancer patients to characterize the localized prostate cancer microenvironment.

Tumor heterogeneity is one of the characteristics of malignant tumors, which can cause differences in tumor growth rate, invasion and metastasis, drug sensitivity, prognosis, etc. Such heterogeneity of single cancer cell expression is potential to decrease the therapeutic efficacy. Thus the understanding of cellular state heterogeneity in human localized prostate cancer may advance cancer immunotherapy research because it shows a possibility that researchers can tailor treatment plans for different causes and phenotypes of tumor heterogeneity relying on the continuous advancement of detection technology. For instance, single-cell gene expression analysis can provide insights for prognostic markers and a theoretical basis for combination immunotherapy.

Immunotherapy for prostate cancer includes cancer vaccine to help patients live several months longer, immune checkpoint inhibitor drugs to retreat people who start growing cancer again after chemotherapy, and chimeric antigen receptor (CAR) therapy.

Except for the application in heterogeneity characterization and exploring cancer immunotherapies, single-cell omics could also be applied in a variety of fields, including cancer, metabolism and neurological diseases, immunology, pharmacogenomics, personalized medicine, and reproductive health, etc., and are widely used to dissect cancer development, unravel cancer evolution, detect rare cells, monitor immunity, profile the tumor microenvironment, discover novel cell types and define states, and other single-cell omics services. Therefore, single-cell omics should be a promise for prostate cancer, breast cancer, and other oncotherapies.