Gene expression signature of Gleason score is associated with prostate cancer outcomes in a radical prostatectomy cohort

Oncotarget
Min A JhunJanet L Stanford

Abstract

Prostate cancer (PCa) is a leading cause of cancer-related mortality worldwide. Gleason score (GS) is one of the best predictors of PCa aggressiveness, but additional tumor biomarkers may improve its prognostic accuracy. We developed a gene expression signature of GS to enhance the prediction of PCa outcomes. Elastic net was used to construct a gene expression signature by contrasting GS 8-10 vs. ≤6 tumors in The Cancer Genome Atlas (TCGA) dataset. The constructed signature was then evaluated for its ability to predict recurrence and metastatic-lethal (ML) progression in a Fred Hutchinson (FH) patient cohort (N=408; NRecurrence=109; NMLprogression=27). The expression signature included transcripts representing 49 genes. In the FH cohort, a 25% increase in the signature was associated with a hazard ratio (HR) of 1.51 (P=2.7×10-5) for recurrence. The signature's area under the curve (AUC) for predicting recurrence and ML progression was 0.68 and 0.76, respectively. Compared to a model with age at diagnosis, pathological stage and GS, the gene expression signature improved the AUC for recurrence (3%) and ML progression (6%). Higher levels of the signature were associated with increased expression of genes in cell cycle-related pat...Continue Reading

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Citations

Mar 15, 2019·Journal of Bioinformatics and Computational Biology·Anna V KudryavtsevaGeorge S Krasnov
Jan 13, 2021·World Journal of Urology·Craig V LabbateScott E Eggener
Apr 14, 2021·BMC Cancer·Ha T N NguyenDaniel Gautheret
Jul 20, 2021·Reports of Biochemistry & Molecular Biology·Mohammad Ghasem KashanizadehAmir Monfaredan
Aug 17, 2021·Briefings in Bioinformatics·Teemu J RintalaVittorio Fortino

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Methods Mentioned

BETA
RNA-seq
biopsy
Assay
PCR

Software Mentioned

Oncotype DX®
Prolaris®
GSEA
Bioconductor
lmtest
GS
Gene Set Enrichment Analysis ( GSEA )
R
glmnet R package
Elastic net

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