Validation of Radiation Response Gene Expression Signatures in High Risk Prostate Cancer

Presenting author:
Niluja Thiruthaneeswaran, MPH, PhD

By Sarah L. Kerns, PhD, MPH, University of Rochester Medical Center

Niluja Thiruthaneeswaran, MPH, PhD, and colleagues at The University of Manchester, United Kingdom, report on validation of two genetic signatures prognostic for seven-year biochemical-relapse free survival (bRFS) in a large (N=478) multi-center cohort of high-risk prostate cancer patients in their abstract The Largest Transcriptomic Resource for Radiotherapy-treated High-risk Prostate Cancer.

Men with high-risk prostate cancer, defined by the National Comprehensive Cancer Network (NCCN) as T3a, Gleason ≥8, or PSA ≥20, comprise approximately 15% of prostate cancer diagnoses but contribute to a disproportionately higher percentage of lethal cases of the disease. The current definition of high-risk includes a heterogeneous group of patients with a range of prognoses, however, improvements in classification are needed to enable more accurate identification of disease likely to recur in order to guide care. Biomarkers such as gene expression signatures are a promising tool to aid in such risk classification. 

All patients in the study led by Dr. Thiruthaneeswaran received intensity modulated radiotherapy (IMRT) as well as androgen deprivation therapy; approximately half also received a high dose rate brachytherapy boost. The investigators generated gene expression data from needle core biopsies using Affymetrix Clariom S arrays, which provide transcriptome-level data including all genes in the human genome.

A previously published hypoxia gene signature, comprising of 32 genes, were confirmed to be prognostic for seven-year bRFS. In addition, they have also validated a radiosensitive index for the first time in a prostate cohort treated with definitive radiotherapy. This study serves as an important validation step critical for moving any biomarker towards clinical use.

In addition to testing these gene signatures, the data generated from this study serve as a valuable resource to the genomics research community for future studies. As noted by the authors, other publicly available transcriptome datasets, such as The Cancer Genome Atlas (TCGA) are dominated by surgical patients and lack the necessary radiotherapy data needed for studies focused on this patient population. Given the comprehensive genomic coverage and detailed clinical data available for this cohort, including radiotherapy dosimetry, the data generated by Dr. Thiruthaneeswaran and colleagues could be used to validate other published gene signatures as well as discover new signatures in a patient population in which biomarkers of aggressive disease and/or treatment response are much needed. The authors note that the data will be made accessible to the research community through the NCBI Gene Expression Omnibus (GEO) data repository. This work provides a critical step toward bringing increasingly personalized care to radiation oncology.

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The Largest Transcriptomic Resource for Radiotherapy-treated High-risk Prostate Cancer was released onDemand in the Science Center on Saturday, October 24, as part of Scientific Session SS 07.

Published on: October 28, 2020


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