Monoclonal Antibody to WHSC1

Total Page:16

File Type:pdf, Size:1020Kb

Monoclonal Antibody to WHSC1 AM50424PU-N OriGene Technologies Inc. OriGene EU Acris Antibodies GmbH 9620 Medical Center Drive, Ste 200 Schillerstr. 5 Rockville, MD 20850 32052 Herford UNITED STATES GERMANY Phone: +1-888-267-4436 Phone: +49-5221-34606-0 Fax: +1-301-340-8606 Fax: +49-5221-34606-11 [email protected] [email protected] Monoclonal Antibody to WHSC1 - Purified Alternate names: KIAA1090, MMSET, Multiple myeloma SET domain-containing protein, NSD2, Nuclear SET domain-containing protein 2, Probable histone-lysine N-methyltransferase NSD2, TRX5, Trithorax-5, Wolf-Hirschhorn syndrome candidate 1 protein Catalog No.: AM50424PU-N Quantity: 0.1 mg Concentration: lot-specific Background: Wolf-Hirschhorn syndrome candidate 1 protein (WHSC1), Nuclear SET domain containing protein 2 (NSD2) is a histone lysine methyltransferase that is deregulated in a subgroup of multiple myelomas. NSD proteins have been described to serve as oncogenes; however, little is known about their targets in transcriptional repression or activation. NSD2 is overexpressed in multiple myelomas via translocation between the NSD2 locus on chromosome 4 and the immunoglobulin locus on chromosome 14. NSD2 is under the regulatory control of this immunoglobulin locus. Further research is required to elucidate its roles and mechanisms in cancer. Uniprot ID: O96028 NCBI: NP_001035889.1 GeneID: 7468 Host / Isotype: Mouse / IgG2b Recommended SM12P, AM03110PU-N Isotype Controls: Clone: 29D1 Immunogen: GST-tagged recombinant protein corresponding to human WHSC1/NSD2. Format: State: Liquid purified Ig fraction Purification: Protein G purified. Buffer System: 0.1 M Tris-Glycine (pH 7.4), 150 mM NaCl with 0.05% sodium azide. Applications: Chromatin Immunoprecipitation: A representative lot was used by an independent laboratory to detect WHSC1/NSD2 in transfected Gal4-reporter/293T cells. (Marango, J., et al. (2008). Blood. 111:3145-3154.) Western Blot: 0.5-1 µg/mL from a representative lot detected WHSC1/NSD2 in 10 µg of HeLa nuclear extract and human placenta tissue lysate. Immunoprecipitation: A representative lot was used by an independent laboratory to detect WHSC1/NSD2 in KMS11 cells. (Marango, J., et al. (2008). Blood. 111:3145-3154.) Other applications not tested. Optimal dilutions are dependent on conditions and should be determined by the user. For research and in vitro use only. Not for diagnostic or therapeutic work. MS/20150619 Material Safety Datasheets are available at www.acris-antibodies.com or on request. Acris Antibodies is now part of the OriGene family. Learn more at www.origene.com 1 / 2 AM50424PU-N: Monoclonal Antibody to WHSC1 - Purified Specificity: Demonstrated to react with Human. Species: Human. Other species not tested. Storage: Store undiluted at 2-8°C. Shelf life: one year from despatch. Pictures: Western Blotting Analysis: Representative lot data. HCT116 cell lysate was probed with Cat. No. AM50424PU-N, Anti-WHSC1/NSD2, clone 29D1 (0.5 µg/mL ). Proteins were visualized using a Goat Anti-Mouse IgG (H+L) secondary antibody conjugated to HRP and a chemiluminescence detection system. Arrow indicates WHSC1/NSD2 (~152 kDa Isoform 1) Western Blotting Analysis: Representative lot data. HeLa nuclear extract (lane 1) and human placenta tissue lysate (lane 2) were probed with Cat. No. AM50424PU-N, Anti- WHSC1/NSD2, clone 29D1 (0.5 µg/mL and 1 µg/mL respectively). Proteins were visualized using a Goat Anti-Mouse IgG (H+L) secondary antibody conjugated to HRP and a chemiluminescence detection system. Arrows indicate WHSC1/NSD2 (~81 kDa Isoform 2 and ~66 kDa Isoform 4) For research and in vitro use only. Not for diagnostic or therapeutic work. MS/20150619 Material Safety Datasheets are available at www.acris-antibodies.com or on request. Acris Antibodies is now part of the OriGene family. Learn more at www.origene.com 2 / 2 Powered by TCPDF (www.tcpdf.org).
Recommended publications
  • Wolf-Hirschhorn Syndrome
    Wolf-Hirschhorn syndrome Author: Dr. Dagmar Wieczorek Creation date: September 2003 Scientific editor: Professor Alain Verloes Institut fur Humangenetik, Universitatsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany. [email protected] Abstract Key words Disease name and synonyms Excluded diseases Diagnostic criteria/ definition Differential diagnosis Frequency Clinical description Management including treatment Etiology Diagnostic methods Genetic counseling Antenatal diagnosis Unresolved questions References Abstract Wolf-Hirschhorn syndrome (WHS) is caused by a deletion of the band 4p16.3 and this deletion may be submicroscopic. The craniofacial phenotype (microcephaly, hypertelorism, prominent glabella, broad and/or beaked nose, short philtrum, micrognathia, downturned corners of the mouth, dysplastic ears, preauricular tags) in combination with mental retardation, seizures, congenital heart defects, genital and renal anomalies is indicative for the diagnosis. A familial translocation is responsible for 5 – 13% of the patients. The remainder of the patients have de novo deletions, usually on the paternal chromosome 4, or de novo translocations in 1.6 %. Submicroscopic deletions require molecular techniques, e.g. microsatellite analysis, or molecular-cytogenetic techniques, e.g. fluorescence in situ hybridisation (FISH), to detect the deletion. Fluorescence in situ hybridisation of the patient and his parents should be performed to confirm/exclude translocations. Recurrence risk is low in de novo deletions and translocations,
    [Show full text]
  • Knockdown of Histone Methyltransferase WHSC1 Induces
    ANTICANCER RESEARCH 39 : 2729-2737 (2019) doi:10.21873/anticanres.13399 Knockdown of Histone Methyltransferase WHSC1 Induces Apoptosis and Inhibits Cell Proliferation and Tumorigenesis in Salivary Adenoid Cystic Carcinoma CHAO LIU 1,2* , YU-HANG JIANG 3* , ZE-LIANG ZHAO 1, HAI-WEI WU 1,2 , LING ZHANG 1, ZHIJIAN YANG 4,5 , ROBERT M. HOFFMAN 4 and JIA-WEI ZHENG 1* 1Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China; 2Department of Oral and Maxillofacial Surgery, Affiliated Shandong Provincial Hospital of Shandong University, Shandong, P.R. China; 3Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai, P.R. China; 4AntiCancer, Inc., San Diego, CA, U.S.A.; 5Origin Biosciences Inc., Nanjing, P.R. China Abstract. Background/Aim: Salivary adenoid cystic by WHSC1 knockdown cells (p<0.05). WHSC1 knockdown carcinoma (SACC) is the most common malignancy of the significantly reduced H3K36me2 modification of the MYC salivary gland with a poor prognosis and survival. The gene promoter in SACC cells and tumorigenesis of SACC present study aimed to investigate the role of histone cells in vivo (p<0.05). Conclusion: Knockdown of WHSC1 methyltransferase WHSC1 in SACC. Materials and Methods: inhibited cell proliferation, induced apoptosis and affected Human SACC specimens were evaluated for WHSC1 tumorigenesis in SACC. expression by RT-PCR and immunohistochemistry. The effects of WHSC1 knockdown on SACC cells proliferation, Salivary adenoid cystic carcinoma (SACC) arises from the cell cycle, clone and tumorsphere formation, and apoptosis secretory epithelial cells of the salivary glands (1) and is the as well as on the expression of related genes were examined.
    [Show full text]
  • Wolf–Hirschhorn Syndrome Candidate 1 Is Involved in the Cellular Response to DNA Damage
    Wolf–Hirschhorn syndrome candidate 1 is involved in the cellular response to DNA damage Ildiko Hajdu, Alberto Ciccia, Susanna M. Lewis, and Stephen J. Elledge1 Department of Genetics, Howard Hughes Medical Institute, Division of Genetics, Brigham and Women’s Hospital, Harvard University Medical School, Boston, MA 02115 Contributed by Stephen J. Elledge, June 22, 2011 (sent for review June 3, 2011) Wolf–Hirschhorn syndrome (WHS) is a malformation syndrome as- neurological impairment. A-T, which is caused by mutations in sociated with growth retardation, mental retardation, and immu- ATM, is characterized by progressive neurologic impairment, nodeficiency resulting from a hemizygous deletion of the short cerebellar ataxia, variable immunodeficiency, and a predisposition arm of chromosome 4, called the WHS critical region (WHSC). The to malignancy (10). Other examples of DDR syndromes that affect WHSC1 gene is located in this region, and its loss is believed to the development and homeostasis of the nervous and immune be responsible for a number of WHS characteristics. We identified system include the Nijmegen breakage syndrome and the ataxia- WHSC1 in a genetic screen for genes involved in responding to telangiectasia–like disorder, which are due to mutations in the replication stress, linking Wolf–Hirschhorn syndrome to the DNA DDR factors NBS1 and MRE11, respectively (11, 12). Mutations damage response (DDR). Here, we report that the WHSC1 protein in ATR, and other components of the ATR pathway, have been is a member of the DDR pathway. WHSC1 localizes to sites of DNA identified in Seckel syndrome patients with microcephaly, facial damage and replication stress and is required for resistance to dysphormism, and growth defects (12).
    [Show full text]
  • Wolf-Hirschhorn Syndrome-Associated Genes Are Enriched in Motile Neural Crest and Affect Craniofacial Development in Xenopus Laevis
    bioRxiv preprint doi: https://doi.org/10.1101/471672; this version posted November 15, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Wolf-Hirschhorn Syndrome-associated genes are enriched in motile neural crest and affect craniofacial development in Xenopus laevis Alexandra Mills1,*, Elizabeth Bearce1,*, Rachael Cella1, Seung Woo Kim1, Megan Selig1, Sangmook Lee1, and Laura Anne Lowery1, 1Boston College, Biology Depart, Chestnut Hill, MA, USA *These authors contributed equally Wolf-Hirschhorn Syndrome (WHS) is a human developmental may hold especially critical roles in this tissue. To this end, disorder arising from a hemizygous perturbation, typically we investigated the roles of four WHS-associated genes a microdeletion, on the short arm of chromosome four. during neural crest cell migration and facial patterning. We In addition to pronounced intellectual disability, seizures, show that during normal development, expression of these and delayed growth, WHS presents with a characteristic genes is enriched in migratory neural crest and craniofacial facial dysmorphism and varying prevalence of microcephaly, structures. Subsequently, we examine their functional roles micrognathia, cartilage malformation in the ear and nose, during facial patterning, cartilage formation, and forebrain and facial asymmetries. These affected craniofacial tissues all derive from a shared embryonic precursor, the cranial neural development, and find that their depletion recapitulates crest, inviting the hypothesis that one or more WHS-affected features of WHS craniofacial malformation. Additionally, genes may be critical regulators of neural crest development two of these genes directly affect neural crest cell migration or migration.
    [Show full text]
  • Transcriptional Regulators Are Upregulated in the Substantia Nigra
    Journal of Emerging Investigators Transcriptional Regulators are Upregulated in the Substantia Nigra of Parkinson’s Disease Patients Marianne Cowherd1 and Inhan Lee2 1Community High School, Ann Arbor, MI 2miRcore, Ann Arbor, MI Summary neurological conditions is an established practice (3). Parkinson’s disease (PD) affects approximately 10 Significant gene expression dysregulation in the SN and million people worldwide with tremors, bradykinesia, in the striatum has been described, particularly decreased apathy, memory loss, and language issues. Though such expression in PD synapses. Protein degradation has symptoms are due to the loss of the substantia nigra (SN) been found to be upregulated (4). Mutations in SNCA brain region, the ultimate causes and complete pathology are unknown. To understand the global gene expression (5), LRRK2 (6), and GBA (6) have also been identified changes in SN, microarray expression data from the SN as familial markers of PD. SNCA encodes alpha- tissue of 9 controls and 16 PD patients were compared, synuclein, a protein found in presynaptic terminals that and significantly upregulated and downregulated may regulate vesicle presence and dopamine release. genes were identified. Among the upregulated genes, Eighteen SNCA mutations have been associated with a network of 33 interacting genes centered around the PD and, although the exact pathogenic mechanism is cAMP-response element binding protein (CREBBP) was not confirmed, mutated alpha-synuclein is the major found. The downstream effects of increased CREBBP- component of protein aggregates, called Lewy bodies, related transcription and the resulting protein levels that are often found in PD brains and may contribute may result in PD symptoms, making CREBBP a potential therapeutic target due to its central role in the interactive to cell death.
    [Show full text]
  • Genetic Testing
    genetic testing PATIENTS.ANSWERS.RESULTS.® aruplab.com/geneticstesting SEPTEMBER 2021 Information in this brochure is current as of September 2021. All content is subject to change. Please contact ARUP Client Services at 800-522-2787 with any questions or concerns. ARUP LABORATORIES As a nonprofit, academic institution of the University of Utah and its Department We believe in of Pathology, ARUP believes in collaborating, sharing knowledge, and contributing to laboratory science in ways that benefit our clients and their patients. collaborating, Our test menu is one of the broadest in the industry, encompassing more sharing than 3,000 tests, including highly specialized and esoteric assays. We offer comprehensive testing in the areas of genetics, molecular oncology, pediatrics, knowledge, and and pain management, among others. contributing ARUP’s clients include many of the nation’s university teaching hospitals to laboratory and children’s hospitals, as well as multihospital groups, major commercial laboratories, and group purchasing organizations. We believe that healthcare science in ways should be delivered as close to the patient as possible, which is why we support your efforts to be the principal healthcare provider in the communities you serve that provide by offering highly complex assays and accompanying consultative support. the best value Offering analytics, consulting, and decision support services, ARUP provides clients with the utilization management tools necessary to prosper in this time of for the patient. value-based care. Our UM+ program helps clients control utilization, reduce costs, Together, and improve patient care. In addition, ARUP is a worldwide leader in innovative laboratory research and development, led by the efforts of the ARUP Institute for ARUP and ® Clinical and Experimental Pathology .
    [Show full text]
  • Oral Manifestations of Wolf-Hirschhorn Syndrome: Genotype-Phenotype Correlation Analysis
    Journal of Clinical Medicine Article Oral Manifestations of Wolf-Hirschhorn Syndrome: Genotype-Phenotype Correlation Analysis Jacobo Limeres 1 , Candela Serrano 1, Joaquin Manuel De Nova 2, Javier Silvestre-Rangil 3, Guillermo Machuca 4 , Isabel Maura 5, Jose Cruz Ruiz-Villandiego 6, Pedro Diz 1,*, Raquel Blanco-Lago 7 , Julian Nevado 8,9,10 and Marcio Diniz-Freitas 1 1 Medical-Surgical Dentistry Research Group (OMEQUI), Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain; [email protected] (J.L.); [email protected] (C.S.); [email protected] (M.D.-F.) 2 Department of Stomatology IV, School of Dentistry, University Complutense de Madrid, 28040 Madrid, Spain; [email protected] 3 Department of Stomatology, University Hospital Doctor Peset-FISABIO, 46017 Valencia, Spain; [email protected] 4 Department of Special Care in Dentistry, School of Dentistry, University of Seville, 41009 Sevilla, Spain; [email protected] 5 Service of Pediatric Dentistry, Barcelona University Children’s Hospital HM Nens, 08009 Barcelona, Spain; [email protected] 6 Service of Special Care in Dentistry, Quirón Hospital, 200012 San Sebastián, Spain; [email protected] 7 Service of Neuropediatrics, University Hospital Central de Asturias, 33011 Oviedo, Spain; [email protected] 8 Medical and Molecular Genetics Institute (INGEMM), La Paz University Hospital, IdiPAZ, 28046 Madrid, Spain; [email protected] 9 Institute of Rare Diseases Research (IIER) & Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain 10 ERN (European Reference Network)-ITHACA, La Paz University Hospital, 28046 Madrid, Spain * Correspondence: [email protected] Received: 24 September 2020; Accepted: 31 October 2020; Published: 4 November 2020 Abstract: Background: Wolf-Hirschhorn syndrome (WHS) is a rare disease caused by deletion in the distal moiety of the short arm of chromosome 4.
    [Show full text]
  • 65127 WHSC1 (D4Z8Q) Rabbit Mab
    Revision 1 C 0 2 - t WHSC1 (D4Z8Q) Rabbit mAb a e r o t S Orders: 877-616-CELL (2355) [email protected] 7 Support: 877-678-TECH (8324) 2 1 Web: [email protected] 5 www.cellsignal.com 6 # 3 Trask Lane Danvers Massachusetts 01923 USA For Research Use Only. Not For Use In Diagnostic Procedures. Applications: Reactivity: Sensitivity: MW (kDa): Source/Isotype: UniProt ID: Entrez-Gene Id: WB, IP H Mk Endogenous 66, 152 Rabbit IgG O96028 7468 Product Usage Information 2. Dolloff, N.G. and Talamo, G. (2013) Adv Exp Med Biol 779, 197-221. 3. Stec, I. et al. (1998) Hum Mol Genet 7, 1071-82. Application Dilution 4. Hudlebusch, H.R. et al. (2011) Clin Cancer Res 17, 2919-33. 5. Yang, S. et al. (2013) Biomarkers 18, 257-63. Western Blotting 1:1000 6. Zhou, P. et al. (2013) Pathol Oncol Res 19, 303-9. Immunoprecipitation 1:200 7. Xiao, M. et al. (2013) J Surg Oncol 107, 428-32. 8. Hudlebusch, H.R. et al. (2011) Cancer Res 71, 4226-35. Storage Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02% sodium azide. Store at –20°C. Do not aliquot the antibody. Specificity / Sensitivity WHSC1 (D4Z8Z) Rabbit mAb recognizes endogenous levels of total WHSC1 protein. Based on antigen sequence, this antibody should detect WHSC1 Isoform II (UniProt O96028-1) and REIIBP (UniProt O96028-4). This antibody does not detect Isoform I (UniProt O96028-3). Species Reactivity: Human, Monkey Source / Purification Monoclonal antibody is produced by immunizing animals with recombinant protein specific to the carboxy terminus of human WHSC1 protein.
    [Show full text]
  • Phenotype Informatics
    Freie Universit¨atBerlin Department of Mathematics and Computer Science Phenotype informatics: Network approaches towards understanding the diseasome Sebastian Kohler¨ Submitted on: 12th September 2012 Dissertation zur Erlangung des Grades eines Doktors der Naturwissenschaften (Dr. rer. nat.) am Fachbereich Mathematik und Informatik der Freien Universitat¨ Berlin ii 1. Gutachter Prof. Dr. Martin Vingron 2. Gutachter: Prof. Dr. Peter N. Robinson 3. Gutachter: Christopher J. Mungall, Ph.D. Tag der Disputation: 16.05.2013 Preface This thesis presents research work on novel computational approaches to investigate and characterise the association between genes and pheno- typic abnormalities. It demonstrates methods for organisation, integra- tion, and mining of phenotype data in the field of genetics, with special application to human genetics. Here I will describe the parts of this the- sis that have been published in peer-reviewed journals. Often in modern science different people from different institutions contribute to research projects. The same is true for this thesis, and thus I will itemise who was responsible for specific sub-projects. In chapter 2, a new method for associating genes to phenotypes by means of protein-protein-interaction networks is described. I present a strategy to organise disease data and show how this can be used to link diseases to the corresponding genes. I show that global network distance measure in interaction networks of proteins is well suited for investigat- ing genotype-phenotype associations. This work has been published in 2008 in the American Journal of Human Genetics. My contribution here was to plan the project, implement the software, and finally test and evaluate the method on human genetics data; the implementation part was done in close collaboration with Sebastian Bauer.
    [Show full text]
  • WHSC1 Enhances DNA Damage Repair Leading to an Increase in Resistance to Chemotherapeutic Agents
    Oncogene (2016), 1–11 © 2016 Macmillan Publishers Limited All rights reserved 0950-9232/16 www.nature.com/onc ORIGINAL ARTICLE MMSET/WHSC1 enhances DNA damage repair leading to an increase in resistance to chemotherapeutic agents MY Shah1,5, E Martinez-Garcia1,5, JM Phillip2, AB Chambliss2, R Popovic1, T Ezponda1, EC Small1, C Will1, MP Phillip2, P Neri3, NJ Bahlis3, D Wirtz2,4 and JD Licht1 MMSET/WHSC1 is a histone methyltransferase (HMT) overexpressed in t(4;14)+ multiple myeloma (MM) patients, believed to be the driving factor in the pathogenesis of this MM subtype. MMSET overexpression in MM leads to an increase in histone 3 lysine 36 dimethylation (H3K36me2), and a decrease in histone 3 lysine 27 trimethylation (H3K27me3), as well as changes in proliferation, gene expression and chromatin accessibility. Prior work linked methylation of histones to the ability of cells to undergo DNA damage repair. In addition, t(4;14)+ patients frequently relapse after regimens that include DNA damage-inducing agents, suggesting that MMSET may play a role in DNA damage repair and response. In U2OS cells, we found that MMSET is required for efficient non-homologous end joining as well as homologous recombination. Loss of MMSET led to loss of expression of several DNA repair proteins, as well as decreased recruitment of DNA repair proteins to sites of DNA double-strand breaks (DSBs). By using genetically matched MM cell lines that had either high (pathological) or low (physiological) expression of MMSET, we found that MMSET-high cells had increased damage at baseline. Upon addition of a DNA-damaging agent, MMSET-high cells repaired DNA damage at an enhanced rate and continued to proliferate, whereas MMSET-low cells accumulated DNA damage and entered cell cycle arrest.
    [Show full text]
  • Characterizing Genetic Drivers of Lymphoma Through High-Throughput Sequencing
    Characterizing Genetic Drivers of Lymphoma through High-Throughput Sequencing by Jenny Zhang University Program in Genetics and Genomics Duke University Date:_______________________ Approved: ___________________________ Sandeep Dave, Supervisor ___________________________ Jen-Tsan Ashley Chi ___________________________ Alexander J. Hartemink ___________________________ Micah A. Luftig Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the University Program in Genetics and Genomics in the Graduate School of Duke University 2016 ABSTRACT Characterizing Genetic Drivers of Lymphoma through High-Throughput Sequencing by Jenny Zhang University Program in Genetics and Genomics Duke University Date:_______________________ Approved: ___________________________ Sandeep Dave, Supervisor ___________________________ Jen-Tsan Ashley Chi ___________________________ Alexander J. Hartemink ___________________________ Micah A. Luftig An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the University Program in Genetics and Genomics in the Graduate School of Duke University 2016 Copyright by Jenny Zhang 2016 Abstract The advent of next-generation sequencing, now nearing a decade in age, has enabled, among other capabilities, measurement of genome-wide sequence features at unprecedented scale and resolution. In this dissertation, I describe work to understand the genetic underpinnings of non-Hodgkin’s lymphoma through exploration
    [Show full text]
  • Use Tumor Suppressor Genes As Biomarkers for Diagnosis Of
    www.nature.com/scientificreports OPEN Use tumor suppressor genes as biomarkers for diagnosis of non‑small cell lung cancer Chuantao Zhang1,3, Man Jiang1,3, Na Zhou1, Helei Hou1, Tianjun Li1, Hongsheng Yu1, Yuan‑De Tan2* & Xiaochun Zhang1* Lung cancer is the leading cause of death worldwide. Especially, non‑small cell lung cancer (NSCLC) has higher mortality rate than the other cancers. The high mortality rate is partially due to lack of efcient biomarkers for detection, diagnosis and prognosis. To fnd high efcient biomarkers for clinical diagnosis of NSCLC patients, we used gene diferential expression and gene ontology (GO) to defne a set of 26 tumor suppressor (TS) genes. The 26 TS genes were down‑expressed in tumor samples in cohorts GSE18842, GSE40419, and GSE21933 and at stages 2 and 3 in GSE19804, and 15 TS genes were signifcantly down‑expressed in tumor samples of stage 1. We used S‑scores and N‑scores defned in correlation networks to evaluate positive and negative infuences of these 26 TS genes on expression of other functional genes in the four independent cohorts and found that SASH1, STARD13, CBFA2T3 and RECK were strong TS genes that have strong accordant/discordant efects and network efects globally impacting the other genes in expression and hence can be used as specifc biomarkers for diagnosis of NSCLC cancer. Weak TS genes EXT1, PTCH1, KLK10 and APC that are associated with a few genes in function or work in a special pathway were not detected to be diferentially expressed and had very small S‑scores and N‑scores in all collected datasets and can be used as sensitive biomarkers for diagnosis of early cancer.
    [Show full text]