title: Meta-analysis of gene expression profiles to predict response to biologic agents in rheumatoid arthritis.
abstract: Our aim was to identify differentially expressed (DE) genes and biological processes that may help predict patient response to biologic agents for rheumatoid arthritis (RA). Using the INMEX (integrative meta-analysis of expression data) software tool, we performed a meta-analysis of publicly available microarray Gene Expression Omnibus (GEO) datasets that examined patient response to biologic therapy for RA. Three GEO datasets, containing 79 responders and 34 non-responders, were included in the meta-analysis. We identified 1,374 genes that were consistently differentially expressed in responders vs. non-responders (651 up-regulated and 723 down-regulated). The up-regulated gene with the smallest p value (p=0.000192) was ASCC2 (Activating Signal Cointegrator 1 Complex Subunit 2), and the up-regulated gene with the largest fold change (average log fold change=-0.75869, p=0.000206) was KLRC3 (Killer Cell Lectin-Like Receptor Subfamily C, Member 3). The down-regulated gene with the smallest p value (p=0.000195) was MPL (Myeloproliferative Leukemia Virus Oncogene). Among the 236 GO terms associated with the set of DE genes, the most significantly enriched was "CTP biosynthetic process" (GO:0006241; p=0.000454). Our meta-analysis identified genes that were consistently DE in responders vs. non-responders, as well as biological pathways associated with this set of genes. These results provide insight into the molecular mechanisms underlying responsiveness to biologic therapy for RA.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1 5 ga, Anam-dong, Seongbuk-gu, Seoul, 136-705, Korea, lyhcgh@korea.ac.kr.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Bae
authors.forename: Gwan Gyu
authors.initials: GG
authors.lastname: Song
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000628:therapy*; D001688:Biological Products / Q000627:therapeutic use*; D018450:Disease Progression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics / Q000379:methods*; D059467:Transcriptome; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products