BACKGROUND INFORMATION: Prostate cancer (PCa) is a common disease but only a small subset of patients are at risk of developing metastasis and lethal disease, and identifying which patients will progress is challenging due to the heterogeneity underlying tumor progression.
Understanding this heterogeneity at the molecular level and the resulting clinical impact is a critical step necessary for risk stratification. Defining genomic fingerprint elucidates molecular variation and may improve prostate cancer risk stratification, providing more accurate prognostic information of tumor aggressiveness (or lethality) for prognostic biomarker development. Therefore, we explored transcriptomic differences between patients with indolent disease outcome and patients who developed metastasis post-radical prostatectomy using genome-wide expression data in the post radical prostatectomy clinical space before metastatic spread.
RESULTS: Based on differential expression analysis, patients with adverse pathological findings who are at higher risk of developing metastasis have a distinct transcriptomic fingerprint that can be detected on surgically removed prostate specimens several years before metastasis detection. Nearly half of the transcriptomic fingerprint features were non-coding RNA highlighting their pivotal role in PCa progression. Protein-coding RNA features in the fingerprint are involved in multiple pathways including cell cycle, chromosome structure maintenance and cytoskeleton organization. The metastatic transcriptomic fingerprint was determined in independent cohorts verifying the association between the fingerprint and metastatic patients. Further, the fingerprint was confirmed in metastasis lesions demonstrating that the fingerprint represents early metastatic transcriptomic changes, suggesting its utility as a prognostic tool to predict metastasis and provide clinical value in the early RP setting.
CONCLUSIONS: Here we show that transcriptomic patterns of metastatic PCa exist that can be detected early after radical prostatectomy. This metastatic fingerprint has potential prognostic ability that can impact PCa treatment management potentially circumventing the requirements for unnecessary therapies.
Written by:
Alshalalfa M, Schliekelman M, Shin H, Erho N, Davicioni E. Are you the author?
GenomeDx Biosciences, Vancouver, BC, Canada.
Reference: Biol Cell. 2015 Apr 21. Epub ahead of print.
doi: 10.1111/boc.201400097
PubMed Abstract
PMID: 25900404