Abstract

Purpose: Gleason score strongly predicts prostate cancer mortality; however, scoring varies among pathologists, and many men are diagnosed with intermediate-risk Gleason score 7. We previously developed a 157-gene signature for Gleason score using a limited gene panel. Using a new whole-transcriptome expression dataset, we verified the previous signature’s performance and developed a new Gleason signature to improve lethal outcome prediction among men with Gleason score 7.

Experimental Design: We generated mRNA expression data from prostate tumor tissue from men in the Physicians’ Health Study and Health Professionals Follow-Up Study (N = 404) using the Affymetrix Human Gene 1.0 ST microarray. The Prediction Analysis for Microarrays method was used to develop a signature to distinguish high (≥8) versus low (≤6) Gleason score. We evaluated the signature’s ability to improve prediction of lethality among men with Gleason score 7, adjusting for 3 + ⁴⁄₄ + 3 status, by quantifying the area under the receiver operating characteristic (ROC) curve (AUC).

Results: We identified a 30-gene signature that best distinguished Gleason score ≤6 from ≥8. The AUC to predict lethal disease among Gleason score 7 men was 0.76 [95% confidence interval (CI), 0.67–0.84] compared with 0.68 (95% CI, 0.59–0.76) using 3 + ⁴⁄₄ + 3 status alone (P = 0.0001). This signature was a nonsignificant (P = 0.09) improvement over our previous signature (AUC = 0.72).

Conclusions: Our new 30-gene signature improved prediction of lethality among men with Gleason score 7. This signature can potentially become a useful prognostic tool for physicians to improve treatment decision making.

Citation

Sinnott JA, Peisch S, Tyekucheva S, Gerke TA, Lis RT, Rider JR, Fiorentino M, Stampfer MJ, Mucci LA, Loda M, Penney KL. Prognostic utility of a new mRNA expression signature of Gleason score. Clin Cancer Res 2017; 23(1): 81--87. PMID: 27663590. PMCID: PMC5215643.