SNPs associated with miRNA expression levels that were also shown to be directly associated with PrCa using a Fisher-test with a significance level of 0.05.

<p>The upper part is from the eQTL dataset, and the lower part is the results for the validation data.</p

Location of the directional test results for the two probabilistic indicies P^H,M,A and P^A,M,H denoted by <i>H</i> < <i>M</i> < <i>A</i> respective <i>A</i> < <i>M</i> < <i>H</i>.

<p>Significant test results that also belong to the 10% most important (Gini Index) miRNAs in the Random Forest run are denoted as HI probes.</p

Each line represents an individual, having a certain expression value for miRNA X.

<p>Independent of the health status of each individual, the expression values are grouped according to the genotype groups of the surrounding SNPs and then tested for differential expression between those groups. (Figure taken from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127427#pone.0127427.ref016" target="_blank">16</a>])</p

Overall classification results of the Random Forest classifier using the severeness measure <i>S</i>_{<i>i</i>,<i>r</i>}.

<p>Overall classification results of the Random Forest classifier using the severeness measure <i>S</i>_{<i>i</i>,<i>r</i>}.</p

Warfarin use and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

<p><b>Objective:</b> Anticoagulants, especially vitamin K antagonists (VKAs) such as warfarin, have been hypothesized to have antitumor properties, and use of VKAs has been associated with a lower prostate cancer (PCa) risk. This study estimated PCa risk among users of warfarin and other anticoagulants.</p> <p><b>Materials and methods:</b> All anticoagulant use among 78,615 men during 1995–2009 was analyzed. Cox regression, adjusted for age, screening trial arm and use of other medications, with medication use as a time-dependent variable, was used to estimate PCa risk overall, and by tumor grade and stage.</p> <p><b>Results:</b> In total, 6537 men were diagnosed with PCa during 1995–2009 (1210 among warfarin users). Compared to non-users, warfarin use was associated with an increased risk of PCa [multivariable-adjusted hazard ratio (HR) = 1.11, 95% confidence interval (CI) 1.01–1.22]. This was limited to short-term, low-dose use, and was not observed in long-term use. A similar overall risk increase was observed for Gleason grade 7–10 PCa. Low-dose, short-term use of warfarin was associated with an increased risk of metastatic PCa. However, the increase in risk vanished with continued use. Compared to other anticoagulants, low-dose use of warfarin was associated with a slightly elevated overall PCa risk (HR = 1.19, 95% CI 1.00–1.43). The increase in risk disappeared in long-term, high-dose use.</p> <p><b>Conclusions:</b> This study, which included a larger number of PCa cases with warfarin exposure than previous studies, does not support previous notions of decreased risk of PCa among warfarin users. A similar risk of PCa was found among warfarin users and the general population, and no difference in risk was found between warfarin and other anticoagulants.</p

Overview of the HI Probes, their target miRNAs with corresponding median expression values and chromosomal position.

<p>Overview of the HI Probes, their target miRNAs with corresponding median expression values and chromosomal position.</p

Heatplot of the HI probes.

<p>Red colours refer to low expression values, whereas green colours represent large expression values for particular probe. The miRNA targeted IDs corresponding to the given probe IDs are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127427#pone.0127427.t001" target="_blank">Table 1</a>. Colors in the dendrogram represent the observed health status (green: healthy, yellow: non-aggr. PrCa, red: aggr.PrCa)</p

AUCs of different ROCs.

<p>Healthy individuals are compared with pooled non-aggressive/aggressive PrCa results (black curve), and aggressive PrCa classifications are compared with the pooled other groups (red).</p

Analysis of ABCA1 and SREBP2 in prostate epithelial cell lines.

<p>The mRNA levels measured by RT-PCR (a and b) and protein levels by Western blotting (c and d). Beta-actin expression is reported in e). The cell lines were treated with DMSO (C) 100 nM Sim (Sim), 50 µg/ml LDL-cholesterol (LDL) or in combination (Sim + LDL) for 48 hours. A double band of 125 kilodaltons (kDa) (precursor form) and 60 kDa (cleaved form) is shown (arrows) for SREBP2 and a 254 kDa band for ABCA1. The ABCA1 and SREBP2 mRNA expression levels were calculated relative to the DMSO-treated (C) samples. RT-PCR results represent the median (bar), lowest and highest (error bars) results of three independent experiments. *p<0.04.</p

A dose-dependent effect of cholesterol on relative cell number of prostate epithelial cell lines.

<p>Number of the treated cells was compared relative to the respective untreated (0) cells after seven days treatment. Results represent the median (bar), lowest and highest (error bars) results of three independent experiments. *p<0.04.</p