Analysis of microarray data is associated with the methodological problems of high dimension and small sample size. Various methods have been used for variable selection in high-dimension and small sample size cases with a single survival endpoint. However, little effort has been directed toward addressing competing risks where there is more than one failure risks. This study compared three typical variable selection techniques including Lasso, elastic net, and likelihood-based boosting for high-dimensional time-to-event data with competing risks. The per-formance of these methods was evaluated via a simulation study by analyzing a real dataset related to bladder cancer patients using time-dependent receiver operator characteristic (ROC) curve and bootstrap .632+prediction error curves. The elastic net penalization method was shown to outper-form Lasso and boosting. Based on the elastic net, 33 genes out of 1381 genes related to bladder cancer were selected. By fitting to the Fine and Gray model, eight genes were highly significant (P< 0.001). Among them, expression of RTN4, SON, IGF1R, SNRPE, PTGR1, PLEK, and ETFDH was associated with a decrease in survival time, whereas SMARCAD1 expression was associated with an increase in survival time. This study indicates that the elastic net has a higher capacity than the Lasso and boosting for the prediction of survival time in bladder cancer patients. Moreover, genes selected by all methods improved the predictive power of the model based on only clinical variables, indicating the value of information contained in the microarray features.

miRNAs are essential factors of an extensively conserved post-transcriptional process controlling gene expression at mRNA level. Varoius biological processes such as growth and differentiation are regulated by miRNAs. Web of Science and PubMed databases were searched using the Endnote software for the publications about the role miRNA-183 family in inner ear: hair cell development and deafness published from 2000 to 2016. A triplet of these miRNAs particularly the miR-183 family is highly expressed in vertebrate hair cells, as with some of the peripheral neurosensory cells. Point mutations in one member of this family, miR-96, underlie DFNA50 autosomal deafness in humans and lead to abnormal hair cell development and survival in mice. In zebrafish, overexpression of the miR-183 family induces extra and ectopic hair cells, while knockdown decreases the number of hair cell. The miR-183 family (miR-183, miR-96 and miR-182) is expressed abundantly in some types of sensory cell in the eye, nose and inner ear. In the inner ear, mechanosensory hair cells have a robust expression level. Despite much similarity of these miRs sequences, small differences lead to distinct targeting of messenger RNAs targets. In the near future, miRNAs are likely to be explored as potential therapeutic agents to repair or regenerate hair cells, cell reprogramming and regenerative medicine applications in animal models because they can simultaneously down-regulate dozens or even hundreds of transcripts.
Animals ; Biological Processes ; Cellular Reprogramming ; Deafness* ; Ear, Inner* ; Gene Expression ; Hair* ; Hearing Loss ; Humans ; Mice ; MicroRNAs ; Models, Animal ; Nose ; Point Mutation ; Regenerative Medicine ; RNA, Messenger ; Triplets ; Vertebrates ; Zebrafish

Cancer of the stomach is the second most frequent cancer-related death worldwide. The survival rate of patients with gastric cancer (GC) remains fragile. There is a requirement to discover biomarkers for prognosis approaches. Helicobacter pylori in the stomach is closely associated with the progression of GC. We identified the genes associated with poor/favorable prognosis in H. pylori–induced GC. Multivariate statistical analysis was applied on the Gene Expression Omnibus (GEO) dataset GSE54397 to identify differentially expressed miRNAs (DEMs) in gastric tissues with H. pylori–induced cancer compared with the H. pylori–positive with non-cancerous tissue. A protein interaction map (PIM) was built and subjected to DEMs targets. The enriched pathways and biological processes within the PIM were identified based on substantial clusters. Thereafter, the most critical genes in the PIM were illustrated, and their prognostic impact in GC was investigated. Considering p-value less than 0.01 and |Log2 fold change| as >1, five microRNAs demonstrated significant changes among the two groups. Gene functional analysis revealed that the ubiquitination system, neddylation pathway, and ciliary process are primarily involved in H. pylori–induced GC. Survival analysis illustrated that the overexpression of DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, and TXNIP was associated with poor prognosis, while increased MRPS5 expression was related to a favorable prognosis in GC patients. DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, TXNIP, and MRPS5 may be considered prognostic biomarkers for H. pylori–induced GC. However, experimental validation is necessary in the future.

Betatrophin is a newly characterized circulating hormone that is produced in tissues such as adipose tissue and liver and stimulates pancreatic beta-cell proliferation. The purpose of the current study was to examine circulating betatrophin levels in Iranian patients with type 2 diabetes mellitus (T2DM) and in normal controls. Seventy-five subjects were enrolled in this case-control study in the following two groups: T2DM patients (n=40) and a group of age-, sex-, and BMI-matched normal control subjects (n=35). Circulating betatrophin concentrations as well as the blood lipid profile, body mass index (BMI), fasting blood sugar (FBS), glycated hemoglobin (HbA1c), and insulin resistance were determined. Circulating betatrophin levels were significantly higher in patients with T2DM than in the normal subjects (4.79+/-1.53 ng/mL vs. 2.79+/-1.11 ng/mL respectively; p=0.001). Serum triacylglycerol and total cholesterol were also significantly higher in patients with T2DM than in the control group. In the patients with T2DM, serum betatrophin was positively correlated with age, FBS, TG, total cholesterol, and HbA1c. The results of this initial study in Iran have shown that circulating betatrophin levels are significantly increased in Iranian patients with T2DM compared with a control group. Additionally, it is postulated that betatrophin as a novel hormone may be involved in the generation of an atherogenic lipid profile.
Adipose Tissue ; Blood Glucose ; Body Mass Index ; Case-Control Studies ; Cholesterol ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Fasting ; Hemoglobin A, Glycosylated ; Humans ; Insulin Resistance ; Iran ; Liver ; Triglycerides

Regulation of the peroxisome proliferator-activated receptor-γ (PPAR-γ) gene plays an important role in controlling the metabolism of lipids and inflammatory processes. Therefore, it can be associated with the pathogenesis of metabolic syndrome (MetS). The purpose of this study was to determine the expression of this gene in peripheral blood mononuclear cells (PBMC) in patients with metabolic syndrome. Using real-time polymerase chain reaction (PCR), mRNA expression of PPAR-γ was found in PBMC from 37 subjects with MetS and 30 healthy controls. Serum levels of glucose and lipid profiles were measured. The total antioxidant capacity (TAC) was measured using the ferric reducing ability of plasma (FRAP) test. Malondialdehyde (MDA) was determined using a fluorimetric method. Total oxidant status (TOS) in serum was assayed according to oxidation of ferric to ferrous in the presence of methyl orange. Super oxide dismutase (SOD) activity was measured using a Randox kit. Expression of PPAR-γ gene was significantly increased in patients with MetS compared to the control subjects (p=0.002). There was no difference in serum levels of TAC, MDA and SOD between the two study groups, but a significant difference was observed in the TOS (p=0.03). Serum levels of triglycerides and glucose were significantly higher in subjects with MetS. According to the results of our study, an increase in the expression of PPAR-γ in subjects with MetS indicated a possible role of PPAR-γ in the pathogenesis of this disease.
Citrus sinensis ; Gene Expression ; Glucose ; Humans ; Malondialdehyde ; Metabolism ; Methods ; Oxidative Stress ; Peroxisomes ; Plasma ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Triglycerides