Potential prostate cancer target identfied by RNA-Seq

Prostate cancer patients have been offered hope after scientists at Newcastle University have identified a new group of molecules that could be targeted to slow tumour growth.

Experts used RNA sequencing to identify hundreds of genes were affected by the male hormone testosterone. It is believed this could lead to new diagnostic tests and treatments.

Among the 700 genes identified was an important set that add sugar groups – known as glycans – to the surface of prostate cancer cells. This group has never been investigated before.

Targeting glycans

 Treatments targeting glycan sugar groups have been developed for other types of the illness, such as breast cancer. It is hoped these treatments could also be used for prostate cancer. Results of the research, published in EBioMedicine, suggest that testosterone changes glycans to make cancer cells more likely to survive, grow and spread to other parts of the body.  Scientists say there is the potential to target these glycans which could stop the growth and spread of tumours and save lives. Dr Jennifer Munkley, Research Associate at the Institute of Genetic Medicine, Newcastle University, co-led the three-year research project with Professor David Elliott.

She said: “Our findings are very significant for future treatments as they identify a new group of molecules in prostate cancer which could be targeted therapeutically. Now we have identified these glycans we will be able to develop strategies to inhibit them and help patients with this condition. Treatments targeting glycan sugar groups have been developed for other types of the illness, such as breast cancer. Our results mean these treatments could also be used for prostate cancer.”

Reciprocal gene expression signatures identify a core set of clinically relevant androgen-regulated target genes

rna-seq

(A) RNA-Seq expression analysis of LNCaP cells treated with or without 10 nM R1881 (a synthetic androgen) for 24 h in triplicate, and of 7 PCa patient prostate biopsies before and after androgen ablation therapy (ADT). Venn diagrams show the number of genes with significant differential expression (q < 0.05). Comparison of the two RNA-Seq datasets identified approximately 700 androgen-regulated genes with reciprocal regulation. 559 genes were up-regulated by androgen treatment in LNCaP cells, but down-regulated in PCa patient samples following ADT (upper Venn diagram). Conversely, 115 genes were down-regulated by androgen addition in LNCaP cells, but up-regulated in PCa patient samples following ADT (lower Venn diagram). (B) Scatter plot of reciprocally regulated genes between the two datasets. The X coordinates are expression log2 fold change values of individual genes in LNCaP cells treated with androgens, relative to cells grown in steroid deplete media. The Y coordinates are log2 fold changes in gene expression of individual genes in the patient dataset after ADT, relative to expression values before treatment. The log2 fold changes were calculated using the relative FPKM values for each gene. (C) Gene Ontology (GO) analysis of the reciprocally regulated genes identified 72 terms with significant gene enrichment (p < 0.05). The top 15 significantly enriched terms are shown in the graph.

Munkley J, Vodak D, Livermore KE, James K, Wilson BT, Knight B, Mccullagh P, Mcgrath J, Crundwell M, Harries LW, Leung HY, Robson CN, Mills IG, Rajan P, Elliott DJ. (2017) Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability. EBioMedicine 8:103-16. [article]

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