The progression of prostate cancer is a complex, multistep process that involves molecular alterations in cells of the tumor and the microenvironment, with associated interactions between the stroma and epithelium. Genomic expression analyses of stromal infiltration markers were performed to determine the significance thereof in prostate cancer.
Genome-wide expression profiles of formalin-fixed, paraffin-embedded radical prostatectomy samples were evaluated from a prospective registry cohort (n = 5239) and 3 retrospective institutional cohorts (n = 1135). Two independent stromal gene expression signatures implied stromal infiltration. Cox proportional hazards regression defined the association between stromal infiltration expression and metastasis-free survival (MFS).
Stromal expression scores were correlated with stromal signature genes and with other key stromal markers (CAV1, VIM, and TAGLN), basal activity, and CD3 and CD4 immune biomarkers (r > 0.5 for all). The top decile of stromal expression was associated with high genomic risk scores (Decipher ≥ 0.6) , high Cancer of the Prostate Risk Assessment-Postsurgical scores, Gleason 9 to 10 disease, and a higher risk for metastasis (hazard ratio, 2.35; 95% CI, 1.37-4.02; P = .001). A higher stromal infiltration score was also associated with decreased expression of DNA repair genes and higher radiation sensitivity genomic scores. Postoperative radiation therapy (RT) was associated with an MFS benefit for patients with high stromal scores, but not for patients with low stromal scores (Pinteraction = .02).
Expression of stromal infiltration markers is correlated with prostate cancer aggressiveness/progression and may be predictive of a response to RT. Stromal infiltration markers should be studied and considered for incorporation into clinical prognostication and decision making.
Cancer. 2020 Jan 06 [Epub ahead of print]
Brandon A Mahal, Mohammed Alshalalfa, Shuang G Zhao, Himisha Beltran, William S Chen, Fallon Chipidza, Elai Davicioni, R Jeffrey Karnes, Sheng-Yu Ku, Tamara L Lotan, Vinayak Muralidhar, Timothy R Rebbeck, Edward M Schaeffer, Daniel E Spratt, Felix Y Feng, Paul L Nguyen
Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts., University of Michigan, Ann Arbor, Michigan., University of California at San Francisco, San Francisco, California., GenomeDx, Inc, San Diego, California., Mayo Clinic, Rochester, Minnesota., Johns Hopkins Medical Institutions, Baltimore, Maryland., Northwestern University, Chicago, Illinois.