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Gene Expression Changes in Progression of Cervical Neoplasia Revealed by microarray Analysis of Cervical Neoplastic Keratinocytes

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JOURNAL OF CELLULAR PHYSIOLOGY 2015年第4期230卷 806-812页

作者： Rotondo, John Charles Bosi, Silvia Bassi, Cristian Ferracin, Manuela Lanza, Giovanni Gafa, Roberta Magri, Eros Selvatici, Rita Torresani, Stefania Marci, Roberto Garutti, Paola Negrini, Massimo Tognon, Mauro Martini, Fernanda Univ Ferrara Dept Morphol Surg & Expt Med I-44121 Ferrara Italy Univ Ferrara Lab Tecnol Terapie Avanzate Tecnopolo Univ Ferrara I-44121 Ferrara Italy Univ Ferrara Dept Med Sci I-44121 Ferrara Italy

To evaluate the gene expression changes involved in neoplastic progression of cervical intraepithelial neoplasia. Using microarray analysis, large-scale gene expression profile was carried out on HPV16-CIN2, HPV16-CIN3, and normal cervical keratinocytes derived from two HPV16-CIN2, two HPV-CIN3 lesions, and two corresponding normal cervical tissues, respectively. Differentially expressed genes were analyzed in normal cervical keratinocytes compared with HPV16-CIN2 keratinocytes and in HPV16-CIN2 keratinocytes compared with HPV16-CIN3 keratinocytes;37 candidate genes with continuously increasing or decreasing expression during CIN progression were identified. One of these genes, phosphoglycerate dehydrogenase, was chosen for further characterization. Quantitative reverse transcription-polymerase chain reaction and immunohistochemical analysis confirmed that expression of phosphoglycerate dehydrogenase consistently increases during progression of CIN toward cancer. Gene expression changes occurring during CIN progression were investigated using microarray analysis, for the first time, in CIN2 and CIN3 keratinocytes naturally infected with HPV16. Phosphoglycerate dehydrogenase is likely to be associated with tumorigenesis and may be a potential prognostic marker for CIN progression. (C) 2014 Wiley Periodicals, Inc.

关键词： CERVICAL intraepithelial neoplasia KERATINOCYTES GENE expression DISEASE progression microarray technology TISSUES -- Wounds & injuries

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A flow-through holed PDMS membrane as a reusable microarray spotter for biomedical assays

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LAB ON A CHIP 2015年第1期15卷 67-71页

作者： Lamberti, A. Angelini, A. Ricciardi, S. Frascella, F. Politecn Torino DISAT Dept Appl Sci & Technol I-10129 Turin Italy

We propose the exploitation of a holed-designed poly(dimethyl)siloxane (PDMS) membrane as an innovative microarray spotter. The membrane is fabricated by a simple technological approach and can be reused several times. A good level of reproducibility is found upon spotting fluorescent proteins at different concentrations over large areas.

关键词： POLYDIMETHYLSILOXANE RESEARCH POLYMERIC membranes microarray technology BIOLOGICAL assay FLUORESCENT proteins

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Semantic Signature: Comparative Interpretation of Gene Expression on a Semantic Space

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COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2016年第1期2016卷 5174503-5174503页

作者： Kim, Jihun Kim, Keewon Kim, Ju Han SNUBI Seoul 110799 South Korea LabGenomics LabGen Clin Res Inst Songnam 463400 South Korea Seoul Natl Univ Coll Med Dept Rehabil Med Seoul 110799 South Korea Seoul Natl Univ Coll Med Dept Biomed Engn Seoul 110799 South Korea Seoul Natl Univ Coll Med Div Biomed Informat Syst Biomed Informat Res Ctr Seoul 110799 South Korea

Background. Interpretation of microarray data remains challenging because biological meaning should be extracted from enormous numeric matrices and be presented explicitly. Moreover, huge public repositories of microarray dataset are ready to be exploited for comparative analysis. This study aimed to provide a platform where essential implication of a microarray experiment could be visually expressed and various microarray datasets could be intuitively compared. Results. On the semantic space, gene sets from Molecular Signature Database (MSigDB) were plotted as landmarks and their relative distances were calculated by Lin's semantic similarity measure. By formal concept analysis, a microarray dataset was transformed into a concept lattice with gene clusters as objects and Gene Ontology terms as attributes. Concepts of a lattice were located on the semantic space reflecting semantic distance from landmarks and edges between concepts were drawn;consequently, a specific geographic pattern could be observed from a microarray dataset. We termed a distinctive geography shared by microarray datasets of the same category as "semantic signature." Conclusions. "Semantic space," a map of biological entities, could serve as a universal platform for comparative microarray analysis. When microarray data were displayed on the semantic space as concept lattices, "semantic signature," characteristic geography for a microarray experiment, could be discovered.

关键词： GENE expression microarray technology COMPARATIVE studies SEMANTICS GENE ontology

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Hybrid Binary Imperialist Competition Algorithm and Tabu Search Approach for Feature Selection Using Gene Expression Data

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BIOMED RESEARCH INTERNATIONAL 2016年第0期2016卷 9721713-9721713页

作者： Wang, Shuaiqun Aorigele Kong, Wei Zeng, Weiming Hong, Xiaomin Shanghai Maritime Univ Informat Engn Coll Shanghai 201306 Peoples R China Toyama Univ Fac Engn Toyama 9308555 Japan

Gene expression data composed of thousands of genes play an important role in classification platforms and disease diagnosis. Hence, it is vital to select a small subset of salient features over a large number of gene expression data. Lately, many researchers devote themselves to feature selection using diverse computational intelligence methods. However, in the progress of selecting informative genes, many computational methods face difficulties in selecting small subsets for cancer classification due to the huge number of genes ( high dimension) compared to the small number of samples, noisy genes, and irrelevant genes. In this paper, we propose a new hybrid algorithm HICATS incorporating imperialist competition algorithm ( ICA) which performs global search and tabu search ( TS) that conducts fine-tuned search. In order to verify the performance of the proposed algorithm HICATS, we have tested it on 10 well-known benchmark gene expression classification datasets with dimensions varying from 2308 to 12600. The performance of our proposed method proved to be superior to other related works including the conventional version of binary optimization algorithm in terms of classification accuracy and the number of selected genes.

关键词： TUMOR classification TUMOR diagnosis LUNG tumors PROSTATE tumors ALGORITHMS BENCHMARKING (Management) GENE expression DATA analysis microarray technology DESCRIPTIVE statistics BRAIN tumor genetics LEUKEMIA genetics TUMOR genetics GENETIC aspects

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The Identification of Microdeletion and Reciprocal Microduplication in 22q11.2 Using High-Resolution CMA technology

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BIOMED RESEARCH INTERNATIONAL 2016年第0期2016卷 7415438-7415438页

作者： Cunha Leite, Ana Julia Pinto, Irene Plaza da Cruz e Cunha, Damiana Mirian Ribeiro, Cristiano Luiz da Silva, Claudio Carlos da Cruz, Aparecido Divino Minasi, Lysa Bernardes Pontificia Univ Catolica Goias Programa Posgrad Mestrado Genet Rua 23540Setor Leste Univ BR-74605050 Goiania Go Brazil Pontificia Univ Catolica Goias Dept Biol Nucleo Pesquisas Replicon Rua 23540Setor Leste Univ BR-74605050 Goiania Go Brazil Univ Fed Goias Programa Posgrad Biotecnol & Biodiversidade Goiania Go Brazil Secretaria Estado Saude Goias Lab Citogenet Humana & Genet Mol Goiania Go Brazil

The chromosome 22q11.2 region has long been implicated in genomic diseases. Some genomic regions exhibit numerous low copy repeats with high identity in which they provide increased genomic instability and mediate deletions and duplications in many disorders. DiGeorge Syndrome is the most common deletion syndrome and reciprocal duplications could be occurring in half of the frequency of microdeletions. We described five patients with phenotypic variability that carries deletions or reciprocal duplications at 22q11.2 detected by Chromosomal microarray Analysis. The CytoScan HD technology was used to detect changes in the genome copy number variation of patients who had clinical indication to global developmental delay and a normal karyotype. We observed in our study three microdeletions and two microduplications in 22q11.2 region with variable intervals containing known genes and unstudied transcripts as well as the LCRs that are often flanking and within this genomic rearrangement. The identification of these variants is of particular interest because it may provide insight into genes or genomic regions that are crucial for specific phenotypic manifestations and are useful to assist in the quest for understanding the mechanisms subjacent to genomic deletions and duplications.

关键词： CHROMOSOME analysis 22Q11 deletion syndrome DIAGNOSIS DIGEORGE syndrome DEVELOPMENTAL disabilities GENETIC techniques MUTATION (Biology) PARENTS FINANCING of research PHENOTYPE FAMILY medical history DATA analysis software microarray technology GENETIC aspects

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Spheroid Culture of Mesenchymal Stem Cells

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STEM CELLS INTERNATIONAL 2016年第1期2016卷 9176357-9176357页

作者： Cesarz, Zoe Tamama, Kenichi Univ Pittsburgh Sch Med Dept Pathol Pittsburgh PA 15261 USA Univ Pittsburgh McGowan Inst Regenerat Med Pittsburgh PA 15219 USA

Compared with traditional 2D adherent cell culture, 3D spheroidal cell aggregates, or spheroids, are regarded as more physiological, and this technique has been exploited in the field of oncology, stem cell biology, and tissue engineering. Mesenchymal stem cells (MSCs) cultured in spheroids have enhanced anti-inflammatory, angiogenic, and tissue reparative/regenerative effects with improved cell survival after transplantation. Cytoskeletal reorganization and drastic changes in cell morphology in MSC spheroids indicate a major difference in mechanophysical properties compared with 2D culture. Enhanced multidifferentiation potential, upregulated expression of pluripotency marker genes, and delayed replicative senescence indicate enhanced stemness in MSC spheroids. Furthermore, spheroid formation causes drastic changes in the gene expression profile of MSC in microarray analyses. In spite of these significant changes, underlying molecular mechanisms and signaling pathways triggering and sustaining these changes are largely unknown.

关键词： MESENCHYMAL stem cells CELL culture TISSUE engineering STEM cell transplantation REGENERATION (Biology) microarray technology THREE-dimensional imaging

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Mitochondria Biogenesis and Bioenergetics Gene Profiles in Isogenic Prostate Cells with Different Malignant Phenotypes

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BIOMED RESEARCH INTERNATIONAL 2016年第0期2016卷 1785201-1785201页

作者： Burch, Tanya C. Rhim, Johng S. Nyalwidhe, Julius O. Eastern Virginia Med Sch Dept Microbiol & Mol Cell Biol 651 Colley AveLester HallSuite 424 Norfolk VA 23507 USA Eastern Virginia Med Sch Leroy T Canoles Jr Canc Res Ctr 651 Colley AveLester HallSuite 424 Norfolk VA 23507 USA Uniformed Serv Univ Hlth Sci Dept Surg 4301 Jones Bridge Rd Bethesda MD 20814 USA

Background. The most significant hallmarks of cancer are directly or indirectly linked to deregulated mitochondria. In this study, we sought to profile mitochondria associated genes in isogenic prostate cell lines with different tumorigenic phenotypes from the same patient. Results. Two isogenic human prostate cell lines RC77N/E ( nonmalignant cells) and RC77T/E ( malignant cells) were profiled for expression of mitochondrial biogenesis and energy metabolism genes by qRT-PCR using the Human Mitochondria and the Mitochondrial Energy Metabolism RT2 PCR arrays. Forty-seven genes were differentially regulated between the two cell lines. The interaction and regulatory networks of these genes were generated by Ingenuity Pathway Analysis. UCP2 was the most significantly upregulated gene in primary adenocarcinoma cells in the current study. The overexpression of UCP2 upon malignant transformation was further validated using human prostatectomy clinical specimens. Conclusions. This study demonstrates the overexpression of multiple genes that are involved in mitochondria biogenesis, bioenergetics, and modulation of apoptosis. These genes may play a role in malignant transformation and disease progression. The upregulation of some of these genes in clinical samples indicates that some of the differentially transcribed genes could be the potential targets for therapeutic interventions.

关键词： ADENOCARCINOMA PROSTATE tumors PROSTATE tumors treatment GLUCOSE analysis RNA analysis ACTIVE oxygen APOPTOSIS BIOLOGICAL assay CELL culture CELL lines COMPARATIVE studies ENERGY metabolism GENE expression GENES LACTATES MITOCHONDRIA POLYMERASE chain reaction PROBABILITY theory FINANCING of research WESTERN immunoblotting PHENOTYPE PHENOMENOLOGICAL biology DISEASE progression DATA analysis software microarray technology DESCRIPTIVE statistics GENETIC aspects

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Lack of an Association between Neutrophil-to-Lymphocyte Ratio and PSA Failure of Prostate Cancer Patients Who Underwent Radical Prostatectomy

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BIOMED RESEARCH INTERNATIONAL 2016年第0期2016卷 6197353-6197353页

作者： Maeda, Yoko Kawahara, Takashi Koizumi, Mitsuyuki Ito, Hiroki Kumano, Yohei Ohtaka, Mari Kondo, Takuya Mochizuki, Taku Hattori, Yusuke Teranishi, Jun-ichi Yumura, Yasushi Miyoshi, Yasuhide Yao, Masahiro Miyamoto, Hiroshi Uemura, Hiroji Yokohama City Univ Med Ctr Dept Urol Yokohama Kanagawa 2320024 Japan Yokohama City Univ Med Ctr Dept Renal Transportat Yokohama Kanagawa 2320024 Japan Yokohama City Univ Grad Sch Med Dept Urol Yokohama Kanagawa 2360004 Japan Johns Hopkins Univ Sch Med Dept Pathol Baltimore MD 21287 USA Johns Hopkins Univ Sch Med Dept Urol Baltimore MD 21287 USA

Introduction. The neutrophil-to-lymphocyte ratio (NLR), which can be easily calculated from routine complete blood counts of the peripheral blood, has been suggested to serve as a prognostic factor for some solid malignancies. In the present study, we aimed to determine the relationship between NLR in prostate cancer patients undergoing radical prostatectomy (RP) and their prognosis. Materials and Methods. We assessed NLR in 73 men (patients) who received RP for their prostate cancer. We also performed immunohistochemistry for CD8 and CD66b in a separate set of RP specimens. Results. The median NLR in the 73 patients was 1.85. There were no significant correlations of NLR with tumor grade (p = 0.834), pathological T stage (p = 0.082), lymph node metastasis (p = 0.062), or resection margin status (p = 0.772). Based on the area under the receiver operator characteristic curve (AUROC) to predict biochemical recurrence after RP, potential NLR cut-off point was determined to be 2.88 or 3.88. However, both of these cut-off points did not precisely predict the prognosis. There were no statistically significant differences in the number of CD66b-positive neutrophils or CD8-positive lymphocytes between stromal tissues adjacent to cancer glands and stromal tissues away from cancer glands and between different grades or stages of tumors. Conclusions. There was no association between NLR and biochemical failure after prostatectomy.

关键词： PROSTATE tumors PROGNOSIS ANTIGENS BLOOD cell count CANCER relapse CHI-squared test IMMUNOHISTOCHEMISTRY LYMPHOCYTES METASTASIS NEUTROPHILS PROSTATECTOMY REFERENCE values (Medicine) FINANCING of research TUMOR classification PROSTATE-specific antigen RECEIVER operating characteristic curves DATA analysis software microarray technology DESCRIPTIVE statistics KAPLAN-Meier estimator LOG-rank test MANN Whitney U Test ONE-way analysis of variance

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The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription

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GASTROENTEROLOGY RESEARCH AND PRACTICE 2016年第1期2016卷 6089658页

作者： Abdel-Rahman, Wael M. Lotsari-Salomaa, Johanna E. Kaur, Sippy Niskakoski, Anni Knuutila, Sakari Jarvinen, Heikki Mecklin, Jukka-Pekka Peltomaki, Paivi Univ Sharjah Coll Hlth Sci Dept Med Lab Sci POB 27272 Sharjah U Arab Emirates SIMR POB 27272 Sharjah U Arab Emirates Univ Helsinki Dept Med & Clin Genet FIN-00290 Helsinki Finland Univ Helsinki Dept Pathol Haartman Inst Helsinki 00029 Hus Finland Univ Helsinki HUSLAB Helsinki 00029 Hus Finland Univ Helsinki Cent Hosp Helsinki 00029 Hus Finland Univ Helsinki Cent Hosp Dept Surg 2 Helsinki 00029 Hus Finland Jyvaskyla Cent Hosp Dept Surg Jyvaskyla 40620 Finland Univ Eastern Finland Inst Clin Med Kuopio Finland

All colorectal cancer cell lines except RKO displayed active beta-catenin/TCF regulated transcription. This feature of RKO was noted in familial colon cancers;hence our aim was to dissect its carcinogenic mechanism. MFISH and CGH revealed distinct instability of chromosome structure in RKO. Gene expression microarray of RKO versus 7 colon cancer lines (with active Wnt signaling) and 3 normal specimens revealed 611 differentially expressed genes. The majority of the tested gene loci were susceptible to LOH in primary tumors with various beta-catenin localizations as a surrogate marker for beta-catenin activation. The immunohistochemistry of selected genes (IFI16, RGS4, MCTP1, DGKI, OBCAM/OPCML, and GLIPR1) confirmed that they were differentially expressed in clinical specimens. Since epigenetic mechanisms can contribute to expression changes, selected target genes were evaluated for promoter methylation in patient specimens from sporadic and hereditary colorectal cancers. CMTM3, DGKI, and OPCML were frequently hypermethylated in both groups, whereas KLK10, EPCAM, and DLC1 displayed subgroup specificity. The overall fraction of hypermethylated genes was higher in tumors withmembranous beta-catenin. We identified novel genes in colorectal carcinogenesis that might be useful in personalized tumor profiling. Tumors with inactive Wnt signaling are a heterogeneous group displaying interaction of chromosomal instability, Wnt signaling, and epigenetics.

关键词： COLON cancer -- Genetic aspects CHROMOSOME abnormalities TRANSCRIPTION factors EPIGENETICS CATENINS GENE expression microarray technology

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Role of miRNAs in Epicardial Adipose Tissue in CAD Patients with T2DM

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BIOMED RESEARCH INTERNATIONAL 2016年第0期2016卷 1629236-1629236页

作者： Liu, Yang Fu, Wenbo Lu, Mu Huai, Shitao Song, Yaqin Wei, Yutao Shihezi Univ Dept Med Shihezi 832000 Xinjiang Peoples R China Peoples Hosp Xinjiang Uygur Autonomous Reg Dept Cardiol Urumqi 830000 Xinjiang Peoples R China Shihezi Univ Affiliated Hosp 1 Sch Med Dept Thorac & Cardiovasc Surg Shihezi 832008 Xinjiang Peoples R China

Background. Epicardial adipose tissue (EAT) is identified as an atypical fat depot surrounding the heart with a putative role in the involvement ofmetabolic disorders, including obesity, type-2 diabetesmellitus, and atherosclerosis. We profiled miRNAs in EAT of metabolic patients with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM) versus metabolically healthy patients by microarray. Compared to metabolically healthy patients, we identified forty-two miRNAs that are differentially expressed in patients with CAD and T2DM from Xinjiang, China. Eleven miRNAs were selected as potential novel miRNAs according to P value and fold change. Then the potential novel miRNAs targeted genes were predicted via TargetScan, PicTar, and miRTarbase, and the function of the target genes was predicted via Gene Ontology (GO) analysis while the enriched KEGG pathway analyses of the miRNAs targeted genes were performed by bioinformatics software DAVID. Then protein-protein interaction networks of the targeted gene were conducted by online software STRING. Finally, using microarray, bioinformatics approaches revealed the possible molecular mechanisms pathogenesis of CAD and T2DM. A total of 11 differentially expressed miRNAs were identified and among them, hsa-miR-4687-3p drew specific attention. Bioinformatics analysis revealed that insulin signaling pathway is the central way involved in the progression of metabolic disorders. Conclusions. The current findings support the fact that miRNAs are involved in the pathogenesis of metabolic disorders in EAT of CAD patients with T2DM, and validation of the results of these miRNAs by independent and prospective study is certainly warranted.

关键词： RNA analysis ACADEMIC medical centers ADIPOSE tissues CELLULAR signal transduction CHI-squared test CORONARY heart disease NON-insulin-dependent diabetes PERICARDIUM PROBABILITY theory FINANCING of research RNA STATISTICS T-test (Statistics) BIOINFORMATICS DATA analysis DATA analysis software microarray technology DESCRIPTIVE statistics

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