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Glinsky. J Cancer Metastasis Treat 2017;3:177-89 Journal of
DOI: 10.20517/2394-4722.2017.43
Cancer Metastasis and Treatment

www.jcmtjournal.com
Original Article Open Access

Malignant field expression signatures in

biopsy samples at diagnosis predict the

likelihood of lethal disease in patients with

localized prostate cancer

Gennadi V. Glinsky

Institute of Engineering in Medicine, University of California, San Diego, CA 92093, USA.
Correspondence to: Dr. Gennadi V. Glinsky, Institute of Engineering in Medicine, University of California, San Diego, 9500 Gilman Dr. MC 0435,
La Jolla, CA 92093, USA. E-mail: gglinskii@ucsd.edu
How to cite this article: Glinsky GV. Malignant field expression signatures in biopsy samples at diagnosis predict the likelihood of lethal disease in
patients with localized prostate cancer. J Cancer Metastasis Treat 2017;3:177-89.
ABSTRACT
Article history: Aim: Overtreatment of early-stage low-risk prostate cancer patients represents a significant
Received: 13 Jun 2017 problem in disease management and has significant socio-economic implications. Changes
Accepted: 30 Aug 2017 in prostate cancer screening and treatment practices in the United States have been
Published: 21 Sep 2017 associated with the recent decline in overall incidence and concomitant significant increase
of the annual incidence of metastatic prostate cancer has been documented. Therefore,
Key words: development of genetic and molecular markers of clinically significant disease in patients
Gene expression signatures, diagnosed with low grade localized prostate cancer would have a major impact in disease
lethal prostate cancer, management. Methods: Identification of gene expression signatures (GES) associated with
localized prostate cancer, lethal prostate cancer has been performed using microarray analyses of biopsy specimens
active surveillance, obtained at the time of diagnosis from 281 patients with Gleason 6 (G6) and G7 tumors
curative interventions, in a Swedish watchful waiting cohort with up to 30 years follow-up. The performance of
clinical management of early- GES has been validated in independent cohort of 568 prostate cancer patients of the Cancer
stage prostate cancer, Genome Anatomy Project Prostate Cancer database. Results: GES comprising 98 genes
malignant field effect identified 89% and 100% of all death events 4 years after diagnosis in G7 and G6 patients,
respectively. At 6 years follow-up, 83% and 100% of all deaths events were captured in
G7 and G6 patients, respectively. Remarkably, the 98-gene signature appears to perform
successfully in patients stratification with as little as 2% of cancer cells in a specimen,
strongly indicating that it captures a malignant field effect in human prostates harboring
cancer cells of different degrees of aggressiveness. In G6 and G7 tumors from prostate
cancer patients of age 65 or younger, GES identified 86% of all death events during the
entire follow-up period. In G6 and G7 tumors from prostate cancer patients of age 70
or younger, GES identified 90% of all death events 6 years after diagnosis. Conclusion:
Classification performance of the reported in this study 98-genes GES of lethal prostate

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