Table 2. Sampling variation reduces the performance of an established lethal outcome-predictive biomarker signature.

Markers: PTEN, SMAD4, CCND1, SPP1	Mean AIC (2.5%, 97.5%)	Median train AUC (2.5%, 97.5%)	Median test AUC (2.5%, 97.5%)
H TMA lethal	282.2 (275.9, 293.2)	0.67 (0.64, 0.70)	0.65 (0.59, 0.74)
L TMA lethal	301.3 (288.6, 316.8)	0.6 (0.58, 0.63)	0.49 (0.42, 0.58)
H TMA aggressiveness	350.1 (330.4, 367.4)	0.62 (0.56, 0.68)	0.56 (0.44, 0.64)
L TMA aggressiveness	381.6 (353.0, 400.7)	0.61 (0.55, 0.68)	0.56 (0.46, 0.65)

Abbreviations: AIC=Akaike information criterion; ROC=receiver-operating characteristic curve; TMA=tissue microarray.

The combination PTEN+SMAD4+CCND1+SPP1 has previously been shown to be prognostic for lethal outcome when measured on prostatectomy tissue. We confirmed that these markers are indeed predictive of lethal outcome when measured in the high-Gleason biopsy simulation tissue (H TMA). However, these markers are unable to predict lethality in the low-Gleason simulation biopsy (L TMA). The markers do not show statistically significant predictive performance for aggressive disease regardless of whether they were measured in high- (H TMA) or low (L TMA)-Gleason tissue areas. C statistic, area under ROC curve.