Novel Gene-Expression Model and Molecular Subtype of Prostate Cancer
Posted: Monday, August 27, 2018
Researchers from several U.S. institutions have developed a novel gene-expression signature, classifier, and decision tree to predict a certain subtype of prostate cancer with an underlying genomic alteration—SPOP (speckle-type POZ protein). Although SPOP-mutant prostate cancer seems to be linked to a higher preoperative prostate-specific antigen (PSA) level, it also appears to be associated with fewer adverse pathologic features and a favorable prognosis.
“We believe this work…reinforces the concept that molecular subtyping of prostate cancer can alter the interpretation of the current standard of care risk stratification methods,” concluded Christopher E. Barbieri, MD, PhD, of Weill Cornell Medical Center, New York, and colleagues in JCO Precision Oncology.
The association between prostate cancer molecular subtypes and clinical outcomes was the focus of the study, with 8,158 patients from retrospective and prospective cohorts included. The investigators’ subclass predictor, which is based on a transcriptional data model, detected about 8% to 9% of cases of SPOP-mutant prostate cancer from both of these cohorts, with “high sensitivity and specificity.” In the past, this prostate cancer subtype was identifiable via DNA sequencing alone; this new model used both RNA sequencing and microarray gene-expression platforms.
Dr. Barbieri and colleagues revealed that the SPOP-mutant subclass was linked to lower frequency of positive margins, extraprostatic extension, and seminal vesicle invasion at prostatectomy. However, a higher pretreatment serum PSA level was also associated with this subtype, based on three independent cohorts. Finally, those with SPOP-mutant prostate cancer, especially those with high-risk preoperative PSA levels, had a favorable prognosis with improved metastasis-free survival.
