Expression Profiling of Hereditary versus Sporadic Prostate Cancer Suggests CYR61, EGR3, KLF6 and SNF1LK as Differentially Expressed Genes

Background: Distinguishing between sub-clinical and aggressive forms of prostate cancer is difficult due to the heterogeneity of the disease. It is, however, important to identify aggressive forms to guide proper treatment. This study compared gene expression profiles in cancer cells from hereditary and sporadic prostate cancer cases and attempted to correlate differentially regulated genes with clinico-pathological characteristics and prognosis. Materials and methods: The study population comprised patients diagnosed with clinically localized prostate cancer undergoing prostatectomy. Patients were divided into hereditary and sporadic cancer cases based on their family history. Fresh frozen biopsies from prostatectomy specimens were laser-dissected for RNA-extraction. Affymetrix HG-U133 Plus GeneChips were used to measure gene expression loaded onto Cluster 3.0 and Ingenuity Pathway Analysis softwares to examine the relationship among genes between groups. Differentially expressed genes were selected for protein expression analysis using immunohistochemistry on histological sections and tissue microarrays. Results: No single genes were signifycantly differentially expressed between hereditary and sporadic cases after adjustment for multiple testing. Using cluster analysis, four transcripts were found to be upregulated in hereditary prostate cancer tissue: CYR61, EGR3, KLF6 and SNF1LK. The intensity of CYR61, EGR2, KLF6 and SNF1LK immunostainings, however, were not significantly different in a separate sample of hereditary and sporadic prostate cancers. Furthermore, no correlations between CYR61, EGR2, KLF6, and SNF1LK staining intensities and the clinico-pathological variables or disease-free survival were detected, except for EGR3 that was significantly associated with T stage (p = 0.04). Conclusion: Overall, no single transcript level was significantly associated with hereditary prostate cancer. Cluster analysis suggested that the expression of CYR61, EGR3, KLF6 and SNF1LK were upregulated in cancer tissue from hereditary cases, but we were not able to confirm this on the protein level, and levels of these proteins were not found to correlate with clinico-pathological characteristics or biochemical recurrence.

A microarray analysis of early activated pathways in concanavalin A-induced hepatitis

Objective:To explore the mechanisms of fulminant hepatitis(FH) in the early stages,and to determine the critical pathways in its initiation and progression.Methods:Twelve BALB/c mice were divided into four groups:one group left as negative control and sacrificed immediately after injection of phosphate-buffered saline(PBS),and another three groups with concanavalin A(Con A) administration sacrificed at 1,3,and 6 h after injection.Affymetrix GeneChip Mouse 430 2.0 Array was employed to evaluate the expression profile of each of the 12 samples.Further analysis was done on the microarray data to extract the genes that were differentially expressed.Enrichment analysis was carried out to determine relevant pathways within which regulated genes were significantly enriched.Results:A total of 393,8354 and 11 344 differentially expressed genes were found,respectively,at three time points.During 0-1 h and 1-3 h,most of the pathways enriched with regulated genes were related to immune response and inflammation,among which Toll-like receptor(TLR) signaling and mitogen-activated protein kinase(MAPK) signaling appeared during both phases,while cytokine-cytokine receptor interaction,apoptosis,T cell receptor signaling,and natural killer(NK) cell-mediated cytotoxicity pathways emerged during the second phase.Pathways found to be significant during 3-6 h were mostly related to metabolic processes.Conclusion:The TLR signaling pathway dominates the early responses of Con A-induced FH in mice.It stimulates the production of type I cytokines,therefore recruiting and activating T/NK cells.Activated T/NK cells exert their cytotoxicity on hepatocytes through inducing death receptorintermediated apoptosis,resulting in liver injury.

The impact of space environment on gene expression in Arabidopsis thaliana seedlings

One of the important questions in space biology is the mechanisms underlying plant responses to an outer space environment,i.e.,how gene expression is altered in space.In this study,the transcriptome of Arabidopsis thaliana seedlings was analyzed as a part of Germany SIMBOX(science in microgravity box)spaceflight experiment on Shenzhou 8 spacecraft.This experiment involved the following treatments:spaceflight with microgravity(Fμg),spaceflight with 1g centrifugal force(F 1g),and ground 1g control(G 1g).Gene chips were used to screen gene expression differences in Arabidopsis thaliana seedlings among these treatments.Microarray analysis revealed that 621 genes were differentially expressed in samples Fμg vs.G 1g,249 genes in samples F 1g vs.G 1g,and 368 genes in samples Fμg vs.F 1g.Gene ontology analysis indicated that the genes were involved in metabolism of stress response,gravitropic response,and DNA damage and repair,suggesting that plants adjust these metabolic pathways to space environmental stress,microgravity,and radiation.

Genome-wide gene expression analysis for target genes to differentiate patients with intestinal tuberculosis and Crohn’s disease and discriminative value of FOXP3 mRNA expression

Background and aims:Crohn’s disease(CD)and intestinal tuberculosis(ITB)are both chronic granulomatous conditions with similar phenotypic presentations.Hence,there is need for a biomarker to differentiate between both these two diseases.This study aimed at genome-wide gene expression analysis of colonic biopsies from confirmed cases of ITB and CD in comparison with controls.To evaluate the role of T regulatory cells,forkhead box P3(FOXP3)mRNA expression was quantified in serum as well as in colonic biopsies from patients with ITB and with the controls.Methods:Paired samples,including serum and colonic biopsies,were taken from 33 study subjects(CD,ITB and controls),and total RNA was extracted.Human whole genome gene expression microarray analysis was performed using the Illumina HumanWG-6 BeadChip Kit with six total RNA samples of the three groups in duplicates.Real-time PCR for FOXP3 mRNA expression was analyzed in serum samples and colonic biopsy samples(4-CD,5-ITB,4-controls).Results:In CD and ITB there was 1.5-fold upregulation of 92 and 382 genes and 1.5-fold downregulation of 91 and 256 genes,respectively.Peroxisome proliferators via the PPARc pathway were most significantly downregulated(P<0.005)in CD.Additionally,the IL4/5/6 signaling pathways and Toll-like receptor signaling pathway were identified as significantly differentially regulated(P<0.005)at>2-fold change.In ITB,the complement activation pathway,specifically the classical pathway,was the most significantly upregulated.FOXP3 mRNA expression was significantly elevated in colonic biopsies obtained from ITB patients as compared with CD cases(4.7062.21 vs 1.4860.31,P=0.016).Conclusions:FOXP3 mRNA expression in colonic mucosa could be a discriminatory marker between ITB and CD.Upregulation of the complement activation pathway in ITB suggests that pathogenetic mechanisms for ITB are similar to those of pulmonary tuberculosis.In CD,downregulation of PPARc was seen in colonic tissue,suggesting that restoration of PPARc-dependent anti-microbial barrier function may be a therapeutic target.