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bioRxiv · 10.1101/040519

Microarray analysis identifies malignant field signatures in biopsy samples at diagnosis predicting the likelihood of lethal disease in patients with localized Gleason 6 and 7 prostate cancer.

Gennadi Glinsky
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Abstract

Overtreatment of early-stage low-risk prostate cancer patients represents a significant problem in disease management and has significant socio-economic implications. Development of genetic and molecular markers of clinically significant disease in patients diagnosed with low grade localized prostate cancer would have a major impact in disease management. A gene expression signature (GES) is reported for lethal prostate cancer in biopsy specimens obtained at the time of diagnosis from patients with Gleason 6 and Gleason 7 tumors in a Swedish watchful waiting cohort with up to 30 years follow-up. A 98-genes GES identified 89% and 100% of all death events 4 years after diagnosis in Gleason 7 and Gleason 6 patients, respectively; at 6 years follow-up, 83% and 100% of all deaths events were captured in Gleason 7 and Gleason 6 patients, respectively. Remarkably, the 98-genes GES 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 Gleason 6 and Gleason 7 tumors from prostate cancer patients of age 65 or younger, GES identified 86% of all death events during the entire follow-up period. In Gleason 6 and Gleason 7 tumors from prostate cancer patients of age 70 or younger, GES identified 90% of all death events 6 years after diagnosis. Classification performance of the reported in this study 98-genes GES of lethal prostate cancer appeared suitable to meet design and feasibility requirements of a prospective 4 to 6 years clinical trial, which is essential for regulatory approval of diagnostic and prognostic tests in clinical setting. Prospectively validated GES of lethal PC in biopsy specimens of Gleason 6 and Gleason 7 tumors will help physicians to identify, at the time of diagnosis, patients who should be considered for exclusion from active surveillance programs and who would most likely benefit from immediate curative interventions.

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Gennadi Glinsky. 2016-02-21. Microarray analysis identifies malignant field signatures in biopsy samples at diagnosis predicting the likelihood of lethal disease in patients with localized Gleason 6 and 7 prostate cancer.. https://doi.org/10.1101/040519

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