A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy

Prostate Cancer (PCA) is the most common malignant disease, and the second leading cause of cancer death in men1. Optimal PCA early detection methods are used to identify patients with high-grade tumors for biopsy and avoid biopsies for those without cancer or low-grade tumors. The research team on this study developed an exosome-derived novel gene expression signature from normalized PCA3 and ERG RNA from urine in order to predict biopsy results. The test doesn’t require pre collection digital rectal examination (DRE); it is collected as part of the clinical workflow2. Exosomes are small double-lipid membrane vesicles that are secreted from cells. They are good for profiling RNA expression from tumor cells, because exosomes are very representative of their origin3.

Pathological exam on biopsies was performed blind to the urine exosome gene expression assay. Exosome diagnostic prostate intelliscore was measured. The urine was collected and stored at 2-8 degrees celsius for 2 weeks. The urine was filtered through 0.8 microliter syringe filter. Samples were normalized for RNA levels with SAM pointed domain containing ETs transcription factor. ERG or PCA3 RNA cycle threshold was derived. Urine exosome gene expression is represented as a number range from 1-100. 499 patients participated in the study. Initial biopsies if PSA from 2.0 to 10.0 ng/ml. PSA level, age, race, family history of PCA were recorded. Primary models and prostate cancer prevention trial risk calculator were compared.

1563 patients had urine samples collected. A 499 patient training cohort was used. Of the 499 255 patients met the intended population (age 50 or older, no prior biopsy, PSA 2-10 ng/ml). The median age for the patients was 62. The median PSA level for the patients was 5.0 ng/ml. The following were risk factors for PCA. 23% of the patients had a suspicious DRE. 25% had a family history of PCA. 19% were African American. PCA was diagnosed in 47%, and 30% had >/= GS7. The exosome diagnostic prostate Intelliscore was used in the training cohort. Urine exosome gene expression assay tSOC and AUC superior to SOC alone for predicting >/= GS6 disease (p<.001). For high grade diesease urine exosome with a cut off of 15.6 showed NPV .96 and PPV .37 for prediction of highgrade. > 15.6 prompts a biopsy, 20% of the biopsies could be prevented, while only 2% of the >/= GS7 PCA.

SOC and PCTRC had poor performance for predicting high grade PCA (AUC .63 and AUC .62). This was derived from genes known to play a role in prostate cancer ERG, PCA3, and SPDEF.

Limitations include the inability to include DRE and free PSA levels.

Authors: James McKierran, Michael Donovan, Vince O’Neil, Stefan Bentink, Mikkel Noerholm, Susan Belzer, Johan Skog, Michael Kattan, Alan Partin, Gerald Andriole, Gordon Brown, John Wei, Ian Thompson Jr., Peter Carroll

Read the Abstract

Reference:

1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA: a cancer journal for clinicians 2014;64:9-29.
2. Donovan MJ, Noerholm M, Bentink S, et al. A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result. Prostate cancer and prostatic diseases 2015;18:370-5.
3. van der Vos KE, Balaj L, Skog J, Breakefield XO. Brain tumor microvesicles: insights into intercellular communication in the nervous system. Cellular and molecular neurobiology 2011;31:949-59.

Login