Relation between Plasma <i>R249S-</i>mutated <i>DNA</i> and HBs-antigen (HBsAg) and HCV-antibody (HCV-ab).

<p><i>X₂</i> test when compared to cholangiocarcinoma, chronic liver disease and reference group all together (*: p value <0.05; ***: p value <0.001; NA: Not Available; ns: non significant).</p

Relation between Plasma <i>R249S-mutated DNA</i> and AFP.

*<p><i>X₂</i> test comparing individuals with <i>R249S</i> > = 150 copies/mL against individuals with <i>R249S</i> <150 copies/mL.</p

Geographic distribution of liver cancer cases.

<p>Dots represent the distribution by province. Pie charts describe the distribution of HCC/no cirrhosis (lines), HCC/cirrhosis (full black) and CC (small dots) among the Northwest, Northeast and Central-south parts of the country.</p

Box and whisker distributions of <i>TP53 R249S</i>-<i>mutated DNA plasma concentrations</i> (≥150 copies/mL) for the different groups.

<p>Boxes extend from 25^th to 75^th percentiles and are divided by a solid line representing the median of each centre. The median levels for the different groups are: 328 in HCC/no cirrhosis, 273 in HCC/cirrhosis, 252 in CC, 256 in CLD and 202 in R.</p

Integrative Genome-Wide Gene Expression Profiling of Clear Cell Renal Cell Carcinoma in Czech Republic and in the United States

<div><p>Gene expression microarray and next generation sequencing efforts on conventional, clear cell renal cell carcinoma (ccRCC) have been mostly performed in North American and Western European populations, while the highest incidence rates are found in Central/Eastern Europe. We conducted whole-genome expression profiling on 101 pairs of ccRCC tumours and adjacent non-tumour renal tissue from Czech patients recruited within the “K2 Study”, using the Illumina HumanHT-12 v4 Expression BeadChips to explore the molecular variations underlying the biological and clinical heterogeneity of this cancer. Differential expression analysis identified 1650 significant probes (fold change ≥2 and false discovery rate <0.05) mapping to 630 up- and 720 down-regulated unique genes. We performed similar statistical analysis on the RNA sequencing data of 65 ccRCC cases from the Cancer Genome Atlas (TCGA) project and identified 60% (402) of the downregulated and 74% (469) of the upregulated genes found in the K2 series. The biological characterization of the significantly deregulated genes demonstrated involvement of downregulated genes in metabolic and catabolic processes, excretion, oxidation reduction, ion transport and response to chemical stimulus, while simultaneously upregulated genes were associated with immune and inflammatory responses, response to hypoxia, stress, wounding, vasculature development and cell activation. Furthermore, genome-wide DNA methylation analysis of 317 TCGA ccRCC/adjacent non-tumour renal tissue pairs indicated that deregulation of approximately 7% of genes could be explained by epigenetic changes. Finally, survival analysis conducted on 89 K2 and 464 TCGA cases identified 8 genes associated with differential prognostic outcomes. In conclusion, a large proportion of ccRCC molecular characteristics were common to the two populations and several may have clinical implications when validated further through large clinical cohorts.</p> </div

Characteristics of the 101 ccRCC patients from the “K2 study” (Czech Republic) included in the whole-genome gene expression microarray study.

*<p>p value calculated using Pearson χ² testing for categorical variables and t-test for continuous variables.</p>**<p>The two younger categories were grouped.</p>***<p>All stage IV patients had distant metastasis at diagnosis, and by definition none of stage I, II or III patients had distant metastasis. Missing stages were due to the lack of lymph nodes and/or metastasis evaluation. Out of 19 cases with missing stage, 9 were pT1a, 7 were pT1b, 1 was pT2a, and 1 was pT3a.</p

Venn diagrams showing the intersection of significant genes differentially downregulated (A) and upregulated (B) in the whole – genome expression profiling microarray dataset (K2) vs. RNA-Sequencing dataset from the Cancer Genome Atlas (TCGA).

<p>Venn diagrams showing the intersection of significant genes differentially downregulated (A) and upregulated (B) in the whole – genome expression profiling microarray dataset (K2) vs. RNA-Sequencing dataset from the Cancer Genome Atlas (TCGA).</p

Characteristics of ccRCC patients in the K2 (Czech Republic) and TCGA (US) series included in survival analysis.

*<p>p value calculated using Pearson χ² testing for categorical variables and t-test for continuous variables.</p>**<p>excluding missing category.</p

Characteristics of the 65 ccRCC patients included in the TCGA series (US) using RNA-Sequencing technology.

<p>Data from all paired tumour/non-tumour sets available on April 19, 2012 were retrieved from TCGA data portal.</p>*<p>p value calculated using Pearson χ² testing for categorical variables and t-test for continuous variables.</p>**<p>the younger two categories were grouped.</p>***<p>excluding missing category.</p>□<p>Of stage IV patients 15 had distant metastasis at diagnosis, and by definition none of stage I, II or III patients had distant metastasis. Missing stages were due to the lack of lymph nodes and/or metastasis evaluation>. These four patients were pT1aNXMX, pT3aNXM0, pT1bNXMX and pT3aNXMX, respectively.</p

Hierarchical Classification of 100 significant differentially expressed genes in K2 series.

<p>Heatmap representing the 50 significant upregulated (in red) and 50 downregulated (in green) probes with the highest fold change following differential expression in ccRCC compared with non-tumour tissue (FDR-adjusted p-value (BH) <0.05, FC ≥2).</p