A 93-gene stroma-derived expression signature predicts metastasis after radical prostatectomy for prostate cancer, researchers report.
"It is important to note that because this signature is stroma derived it may mitigate the problems associated with intertumor heterogeneity that is so common in prostate cancer and plagues tumor-targeted biopsies,” Dr. Colin C. Collins from the University of British Columbia, in Vancouver, Canada, told Reuters Health by email.
Both intertumor and intratumor heterogeneity complicate patient stratification and biomarker discovery. Patient-derived xenografts, which make it possible to segregate the gene signature of cancer cells and that of cancer-associated stromal cells, may facilitate the identification of potential biomarkers predictive of metastasis, according to Dr. Collins and colleagues.
The team used whole-genome and whole-transcriptome sequencing on five prostate-cancer patient-derived murine xenograft models to develop a prognostic signature for distinguishing indolent from aggressive prostate cancer.
While genomic and transcriptomic profiles of tumor cells were not associated with varying metastatic abilities, profiles of stromal cells were able to distinguish between metastatic and non-metastatic models, the researchers report in European Urology, online March 19.
From 124 differentially expressed murine stromal genes, a generalized linear model identified a 93-gene stroma-derived metastasis signature (SDMS).
When tested in five independent cohorts of patients with primary prostate tumors containing 856 patients in all, higher SDMS scores significantly predicted metastasis independent of clinical and pathological variables.
SDMS improved the accuracy of three previously reported gene signatures in detecting metastasis within five years following radical prostatectomy, suggesting that the SDMS captures additional prognostic information and could improve the predictive power of those signatures.
“If implemented in combination with other established biomarkers and clinicopathological factors, this SDMS could provide invaluable information to facilitate better prostate cancer patient management,” the researchers conclude.
“This signature may increase the confidence of physicians counseling patients on active surveillance and other treatment options for prostate cancer,” Dr. Collins said.
The study did not have commercial funding; GenomeDx Biosciences employed three of the 33 authors.