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Detection of lung cancer at an early stage by sensitive screening tests could be an important strategy to improving prognosis. Our objective was to identify a panel of circulating microRNAs in plasma that will contribute to early detection of lung cancer. Plasma samples from 100 early stage (I to IIIA) non-small-cell lung cancer (NSCLC) patients and 100 non-cancer controls were screened for 754 circulating microRNAs via qRT-PCR, using TaqMan MicroRNA Arrays. Logistic regression with a lasso penalty was used to select a panel of microRNAs that discriminate between cases and controls. Internal validation of model discrimination was conducted by calculating the bootstrap optimism-corrected AUC for the selected model. We identified a panel of 24 microRNAs with optimum classification performance. The combination of these 24 microRNAs alone could discriminate lung cancer cases from non-cancer controls with an AUC of 0.92 (95% CI: 0.87-0.95). This classification improved to an AUC of 0.94 (95% CI: 0.90-0.97) following addition of sex, age and smoking status to the model. Internal validation of the model suggests that the discriminatory power of the panel will be high when applied to independent samples with a corrected AUC of 0.78 for the 24-miRNA panel alone. Our 24-microRNA predictor improves lung cancer prediction beyond that of known risk factors.

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.

The quality of tissue samples and extracted mRNA is a major source of variability in tumor transcriptome analysis using genome-wide expression microarrays. During and immediately after surgical tumor resection, tissues are exposed to metabolic, biochemical and physical stresses characterized as \"warm ischemia\". Current practice advocates cryopreservation of biosamples within 30 minutes of resection, but this recommendation has not been systematically validated by measurements of mRNA decay over time. Using Illumina HumanHT-12 v3 Expression BeadChips, providing a genome-wide coverage of over 24,000 genes, we have analyzed gene expression variation in samples of 3 hepatocellular carcinomas (HCC) and 3 lung carcinomas (LC) cryopreserved at times up to 2 hours after resection. RNA Integrity Numbers (RIN) revealed no significant deterioration of mRNA up to 2 hours after resection. Genome-wide transcriptome analysis detected non-significant gene expression variations of -3.5%/hr (95% CI: -7.0%/hr to 0.1%/hr; p = 0.054). In LC, no consistent gene expression pattern was detected in relation with warm ischemia. In HCC, a signature of 6 up-regulated genes (CYP2E1, IGLL1, CABYR, CLDN2, NQO1, SCL13A5) and 6 down-regulated genes (MT1G, MT1H, MT1E, MT1F, HABP2, SPINK1) was identified (FDR <0.05). Overall, our observations support current recommendation of time to cryopreservation of up to 30 minutes and emphasize the need for identifying tissue-specific genes deregulated following resection to avoid misinterpreting expression changes induced by warm ischemia as pathologically significant changes.

Purpose: Findings from epidemilogical studies examining physical activity in relation to pancreatic cancer risk have suggested decreased risks for physical activity; however, the results are inconsistent. Methods: The association between occupational and leisure-time physical activity and risk of pancreatic cancer was examined among 826 pancreatic cancer cases and 930 age-, sex- and center-matched controls from a large multicenter central European study in Czech Republic and Slovakia recruited between 2004 and 2012. Data on physical activity including type and dose (frequency, intensity, and duration) were examined using multivariable-adjusted logistic regression models. Results: Occupational physical activity was not significantly associated with risk of pancreatic cancer [odds ratio (OR) 0.90, 95 % confidence interval (CI) 0.71–1.15]. A 35 % decrease in risk of pancreatic cancer was observed for regular leisure-time physical activity (OR 0.65, 95 % CI 0.52–0.87). The risk estimates were significant for low and moderate intensity of activity with the strongest protective effect among individuals who exercised during more than 40 weeks per year. The results for cumulated leisure-time physical activity assessed 1 year prior to diagnosis achieved the same level of risk reduction. In addition, stronger risk estimates for leisure-time physical activity were observed among women (men: OR 0.74, 95 % CI 0.54–1.01; women: OR 0.53, 95 % CI 0.37–0.75). The findings for female participants were stronger for intensity and frequency of leisuretime physical activity, in particular for light and moderate activity (OR 0.43, 95 % CI 0.25–0.75; and OR 0.57, 95 % CI 0.37–0.88, respectively). Conclusion: These results provide evidence for a decreased risk of pancreatic cancer associated with regular leisure-time physical activity.

Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) and cutaneous peripheral T-cell lymphoma not otherwise specified (C-PTL-NOS) are cutaneous T-cell lymphomas with distinct clinical behaviors. Whereas C-ALCL has a favorable prognosis with frequent spontaneous disease regression, C-PTL-NOS runs a more aggressive course. The molecular pathogenesis of these cutaneous T-cell lymphoma types has not yet been studied in detail. In this issue, van Kester et al. report new imbalances that could contribute to our understanding of the differences between these two lymphoma types.

The incidence of renal cell carcinoma (RCC) is increasing worldwide, and its prevalence is particularly high in some parts of Central Europe. Here we undertake whole-genome and transcriptome sequencing of clear cell RCC (ccRCC), the most common form of the disease, in patients from four different European countries with contrasting disease incidence to explore the underlying genomic architecture of RCC. Our findings support previous reports on frequent aberrations in the epigenetic machinery and PI3K/mTOR signalling, and uncover novel pathways and genes affected by recurrent mutations and abnormal transcriptome patterns including focal adhesion, components of extracellular matrix (ECM) and genes encoding FAT cadherins. Furthermore, a large majority of patients from Romania have an unexpected high frequency of A:T>T:A transversions, consistent with exposure to aristolochic acid (AA). These results show that the processes underlying ccRCC tumorigenesis may vary in different populations and suggest that AA may be an important ccRCC carcinogen in Romania, a finding with major public health implications. Renal cancer accounts for 2.4% of all adult cancers and its incidence is increasing worldwide. Here, the authors carry out genome and transcriptome sequencing of clear cell renal cell carcinomas (ccRCCs) and highlight genomic aberrations and biological pathways underlying ccRCC tumorigenesis.

Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10-4). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10-3) and LUSC (p = 9x10-4) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10-48 and p = 3x10-29 in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.

The quality of tissue samples and extracted mRNA is a major source of variability in tumor tran0.05). Overall, our observations support current recommendation of time to cryopreservation of up to 30 minutes and emphasize the need for identifying tissue-specific genes deregulated following resection to avoid misinterpreting expression changes induced by warm ischemia as pathologically significant changes.

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 greater than or equal to 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.

Forest biomass is a renewable source of environmentally friendly material—wood. However, wood processing generates large amounts of by-products, including branches. These byproducts are often used as firewood; however, they can be used much more effectively. In this study, the pyrolysis of two woods, namely birch and pine, was proposed. The liquid products of pyrolysis were studied by FTIR spectroscopy, and the heating value of these products was evaluated. In order to find the optimal pyrolysis temperature from the point of view of the calorific value of the product, the process was carried out at four temperatures: 450, 500, 550, and 600 °C. The liquid product yielded three fractions, from which two were analyzed, namely the dense tar fraction and light liquid fraction. FTIR analysis results clearly demonstrated that samples from different fractions differ from one another, yet the results within the same fraction are remarkably similar. The tar fraction was characterized with a higher gross calorific value between 42 to 50 MJ/kg, while the liquid fraction gross calorific value was between 29 and 39 MJ/kg; in general, pine wood yielded products with higher calorific values. The pyrolysis of small wood industry by-products is an interesting method of utilization, yielding not only a liquid product with good calorific properties, but also a solid product, namely biochar, which may be used in carbon storage or used as a soil amendment.