In contrast, the tumor samples from patients 2, 3, and 6 do not fall into the same major cluster or terminal cluster as the matched benign samples.
A linear modelling approach was used to estimate the expression of each probe in the five subtypes, and the set of matched benign samples.
They detected many more events in cancer samples than in matched benign samples, and a large fraction of their detected events were either specific to, or had a much higher expression level in, the cancer samples.
Previous studies have observed similar trends in PCa, with increased CD147 expression in PCa samples compared to matched benign samples and an association with poor prognosis after prostatectomy [ 9– 13].
The expression levels of the majority of the profiled ADAMs, namely ADAM8, 9, 10, 12, 15 and 17, were increased significantly in malignant OG tissue compared with matched benign samples (Table 2).
Genes with the greatest relative increase in expression in malignant tissue were MMP1, 3, 7, 9, 10, 11, 12, 16 and 24 (P<0.01), each of which demonstrated a median relative gene expression >4-fold than that of matched benign samples.
Therefore using our cohort of cases with multiple tumour foci and matched benign samples, we found that hypermethylation at the HES5 promoter region was observed across tumour samples from all patients and in all spatially separated tumour foci from the same patient.
The five-ratio test was then examined in an independent set of 13 matched benign bladder urothelium samples and bladder cancer samples (n = 26 samples total) using quantitative RT-PCR.
We assessed the reproducibility and clonality of these eight differentially methylated regions in our cohort of cases with multiple spatially separate tumour samples, matched benign tissue and blood DNA samples (Fig. 1b and Supplementary Figure 1f, g, h, i, j, k, l, m).
The present investigation was restricted to comparison of expression in matched benign versus cancer samples.
