Publication

Identification of a candidate gene panel for the early diagnosis of prostate cancer

Identification of a 3-gene panel for the detection of clinically significant prostate cancer

 

Leyten G et al. Clin Cancer Res 2015;21:3061-70 

 

What was studied?

This study identified 3 significant genes that could be used as prostate cancer-specific biomarkers for the detection of high-grade (Gleason score ≥7) prostate cancer.

 

What were the main outcomes?

A 3-gene panel was identified that was associated with the identification of significant high-grade prostate cancer: HOXC6, TDRD1 and DLX1. This gene panel can be assessed in urinary sediments. It had a higher accuracy to predict high-grade prostate cancer than either PSA or PCA3 (Table). However, when this gene panel was combined with PSA, the predictive accuracy was further improved (Table). The predictive accuracy of the 3-gene panel remained constant across several PSA cut-off values.

 

Table. Predictive accuracy for high-grade (Gleason score ≥7) prostate cancer

AUC

3-gene panel

3-gene panel + PSA

PSA

PCA3

 

0.77

0.81

0.72

0.68

     

What was concluded?

The 3-gene panel (HOXC6, TDRD1 and DLX1) represents a promising, new biomarker tool to identify men at risk of clinically significant prostate cancer. The combination with PSA bears great potential for the early diagnosis of high-grade prostate cancer. The current controversy in early detection of prostate cancer stems from finding indolent cancers and treating them with associated morbidities. These biomarkers address that concern by identifying clinically significant cancers.

 

How was the study performed?

A stepwise selection of a panel of biomarkers for the detection of high-grade prostate cancer was performed. Gene expression profiling was performed on snap-frozen micro-dissected tissue specimens. The 39 most promising genes were tested on another set of tissue specimens using quantitative polymerase chain reaction (qPCR). The 34 biomarkers that could discriminate prostate cancer from normal prostate were tested on a small set of 16 urinary sediments. The 8 genes that could best detect prostate cancer in urinary sediments were selected and tested in 358 urinary sediments of an intention-to-treat cohort. This resulted in a urinary 3-gene panel to predict high-grade prostate cancer in biopsies. 

 

Editor comment

There is persistent controversy concerning detection and treatment of prostate cancer. There is a pressing need to develop a method to detect prostate cancers that represent a significant risk to men. Numerous organizations have examined the risk and benefits of screening and concluded that the risks outweigh the benefits. This test offers a way forward by identifying men who have clinically significant cancer. We need to incorporate this into our algorithm.

Photo Prof. David Crawford
Prof. E. David Crawford
University of Colorado, Denver, CO, USA

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