title: RNA-Seq for Gene Expression Profiling of Human Necrotizing Enterocolitis: a Pilot Study.
abstract: Necrotizing enterocolitis (NEC) characterized by inflammatory intestinal necrosis is a major cause of mortality and morbidity in newborns. Deep RNA sequencing (RNA-Seq) has recently emerged as a powerful technology enabling better quantification of gene expression than microarrays with a lower background signal. A total of 10 transcriptomes from 5 pairs of NEC lesions and adjacent normal tissues obtained from preterm infants with NEC were analyzed. As a result, a total of 65 genes (57 down-regulated and 8 up-regulated) revealed significantly different expression levels in the NEC lesion compared to the adjacent normal region, based on a significance at fold change ≥ 1.5 and P ≤ 0.05. The most significant gene, DPF3 (P < 0.001), has recently been reported to have differential expressions in colon segments. Our gene ontology analysis between NEC lesion and adjacent normal tissues showed that down-regulated genes were included in nervous system development with the most significance (P = 9.3 × 10⁻⁷; P(corr) = 0.0003). In further pathway analysis using Pathway Express based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, genes involved in thyroid cancer and axon guidance were predicted to be associated with different expression (P(corr) = 0.008 and 0.020, respectively). Although further replications using a larger sample size and functional evaluations are needed, our results suggest that altered gene expression and the genes' involved functional pathways and categories may provide insight into NEC development and aid in future research.
authors.affiliation: Department of Surgery, Jeju National University Hospital, Jeju, Korea.
authors.forename: Kyuwhan
authors.identifier: http://orcid.org/0000-0001-5997-4975
authors.initials: K
authors.lastname: Jung
authors.affiliation: Department of Physiology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Insong
authors.identifier: http://orcid.org/0000-0001-6896-9748
authors.initials: I
authors.lastname: Koh
authors.affiliation: Research Institute for Basic Science, Sogang University, Seoul, Korea.
authors.forename: Jeong Hyun
authors.identifier: http://orcid.org/0000-0003-4879-0075
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea.
authors.forename: Hyun Sub
authors.identifier: http://orcid.org/0000-0003-1749-6172
authors.initials: HS
authors.lastname: Cheong
authors.affiliation: Department of Surgery, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Taejin
authors.identifier: http://orcid.org/0000-0002-8508-2353
authors.initials: T
authors.lastname: Park
authors.affiliation: Department of Surgery, Donga University Hospital, Busan, Korea.
authors.forename: So Hyun
authors.identifier: http://orcid.org/0000-0003-3757-4684
authors.initials: SH
authors.lastname: Nam
authors.affiliation: Department of Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Soo Min
authors.identifier: http://orcid.org/0000-0002-2636-8028
authors.initials: SM
authors.lastname: Jung
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Cherry Ann
authors.identifier: http://orcid.org/0000-0003-0273-8239
authors.initials: CA
authors.lastname: Sio
authors.affiliation: Department of Surgery, Donga University Hospital, Busan, Korea.
authors.forename: Su Yeong
authors.identifier: http://orcid.org/0000-0001-6463-0210
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Neonatology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Euiseok
authors.identifier: http://orcid.org/0000-0003-0693-5627
authors.initials: E
authors.lastname: Jung
authors.affiliation: Department of Neonatology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Byoungkook
authors.identifier: http://orcid.org/0000-0001-5435-606X
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Neonatology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Hye Rim
authors.identifier: http://orcid.org/0000-0001-6445-5934
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Eun
authors.identifier: http://orcid.org/0000-0003-0624-8149
authors.initials: E
authors.lastname: Shin
authors.affiliation: Department of Pediatric Surgery, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Sung Eun
authors.identifier: http://orcid.org/0000-0003-3155-2900
authors.initials: SE
authors.lastname: Jung
authors.affiliation: Department of Neonatology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Chang Won
authors.identifier: http://orcid.org/0000-0003-1911-0253
authors.initials: CW
authors.lastname: Choi
authors.affiliation: Department of Neonatology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Beyong Il
authors.identifier: http://orcid.org/0000-0003-0408-9279
authors.initials: BI
authors.lastname: Kim
authors.affiliation: Department of Surgery, Gyemyoung University Dongsan Hospital, Daegu, Korea.
authors.forename: Eunyoung
authors.identifier: http://orcid.org/0000-0002-8884-1642
authors.initials: E
authors.lastname: Jung
authors.affiliation: Research Institute for Basic Science, Sogang University, Seoul, Korea.|Department of Life Science, Sogang University, Seoul, Korea. hdshin@sogang.ac.kr.
authors.forename: Hyoung Doo
authors.identifier: http://orcid.org/0000-0003-1732-7838
authors.initials: HD
authors.lastname: Shin
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D020345:Enterocolitis, Necrotizing / Q000235:genetics / Q000473:pathology*; D005865:Gestational Age; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D010865:Pilot Projects; D012313:RNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; C452161:DPF3 protein, human; D014157:Transcription Factors; D012313:RNA
keywords: Gene Expression; Necrotizing Enterocolitis; RNA-Seq