Network-based gene deletion analysis identifies candidate genes and molecular mechanism involved in clear cell renal cell carcinoma.

Human clear cell renal cell carcinoma (ccRCC) is the most common and frequently occurring histological subtype of RCC. Unlike other carcinomas, candidate predictive biomarkers for this type are in need to explore the molecular mechanism of ccRCC and identify candidate target genes for improving disease management. For this, we chose case-control-based studies from the Gene Expression Omnibus and subjected the gene expression microarray data to combined effect size meta-analysis for identifying shared genes signature. Further, we constructed a subnetwork of these gene signatures and evaluated topological parameters during the gene deletion analysis to get to the central hub genes, as they form the backbone of the network and its integrity. Parallelly, we carried out functional enrichment analysis using gene ontology and Elsevier disease pathway collection. We also performed microRNAs target gene analysis and constructed a regulatory network. We identified a total of 577 differentially expressed genes (DEGs), where 146 overexpressed and 431 underexpressed with a significant threshold of adjusted P values <0.05. Enrichment analysis of these DEGs' functions showed a relation to metabolic and cellular pathways like metabolic reprogramming in cancer, proteins with altered expression in cancer metabolic reprogramming, and glycolysis activation in cancer (Warburg effect). Our analysis revealed the potential role of PDHB and ATP5C1 in ccRCC by altering metabolic pathways and amyloid beta precursor protein (APP) role in altering cell-cycle growth for the tumour progression in ccRCC conditions. Identification of these candidate predictive genes paves the way for the development of biomarker-based methods for this carcinoma.

Screening for obesity in the offspring of first-cousin consanguineous couples: A Phase-I study in Saudi Arabia.

Consanguineous or cousin marriages are very common in Saudi Arabia. However, owing to limited studies and insufficient knowledge about genetic diseases/disorders, many couples are unaware of the increased health risks for their offspring. Among the inherited and complex diseases from parents' consanguinity, obesity is common; therefore, we examined the prevalence of obesity in the offspring of first-cousin consanguineous couples in Saudi Arabia. In this questionnaire-based study, 657 individuals (mean age = 18.7 ±â€¯10.2 years; age range = 2-65 years) who were residing in Riyadh, Saudi Arabia participated. Among them, almost 90% were native Saudis. Participants mean body mass index (BMI) was 24.5 ±â€¯9.1 kg/m2. Sex- stratified demographic details confirmed a significant association between age and BMI (p < .001). We confirmed that adolescents and adults were more prone to develop obesity. Adults and non-Saudi participants were three times more likely to develop obesity if they had first-cousin consanguineous parents than those who did not. Of the 30% of participants who were obese, 100 will be selected for Phase II, in which we plan to perform exome sequencing.

Differential Gene Expression in Peripheral White Blood Cells with Permissive Underfeeding and Standard Feeding in Critically Ill Patients: A Descriptive Sub-study of the PermiT Randomized Controlled Trial.

The effect of short-term caloric restriction on gene expression in critically ill patients has not been studied. In this sub-study of the PermiT trial (Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Trial- ISRCTN68144998), we examined gene expression patterns in peripheral white blood cells (buffy coat) associated with moderate caloric restriction (permissive underfeeding) in critically ill patients compared to standard feeding. Blood samples collected on study day 1 and 14 were subjected to total RNA extraction and gene expression using microarray analysis. We enrolled 50 patients, 25 in each group. Among 1751 tested genes, 332 genes in 12 pathways were found to be significantly upregulated or downregulated between study day 1 and 14 (global p value for the pathway ≤ 0.05). Using the heatmap, the differential expression of genes from day 1 to 14 in the permissive underfeeding group was compared to the standard feeding group. We further compared gene expression signal intensity in permissive underfeeding compared standard feeding by constructing univariate and multivariate linear regression models on individual patient data. We found differential expression of several genes with permissive underfeeding, most notably those related to metabolism, autophagy and other cellular functions, indicating that moderate differences in caloric intake trigger different cellular pathways.