title: ADAM28: a potential oncogene involved in asbestos-related lung adenocarcinomas.
abstract: Asbestos-related lung cancer accounts for 4-12% of all lung cancers worldwide. Since putative mechanisms of carcinogenesis differ between asbestos and tobacco induced lung cancers, tumors induced by the two agents may be genetically distinct. To identify gene expression biomarkers associated with asbestos-related lung tumorigenicity we performed gene expression array analysis on tumors of 36 patients with primary lung adenocarcinoma, comparing 12 patients with lung asbestos body counts above levels associated with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma) with 24 patients with no asbestos bodies (NARLC-AC: non-asbestos related lung cancer-adenocarcinoma). Genes differentially expressed between ARLC-AC and NARLC-AC were identified on fold change and P value, and then prioritized using gene ontology. Candidates included ZNRF3, ADAM28, PPP1CA, IRF6, RAB3D, and PRDX1. Expression of these six genes was technically and biologically replicated by qRT-PCR in the training set and biologically validated in three independent test sets. ADAM28, encoding a disintegrin and metalloproteinase domain protein that interacts with integrins, was consistently upregulated in ARLC across all four datasets. Further studies are being designed to investigate the possible role of this gene in asbestos lung tumorigenicity, its potential utility as a marker of asbestos related lung cancer for purposes of causal attribution, and its potential as a treatment target for lung cancers arising in asbestos exposed persons.
authors.affiliation: School of Medicine, The University of Queensland, QLD, Australia.
authors.forename: Casey M
authors.initials: CM
authors.lastname: Wright
authors.forename: Jill E
authors.initials: JE
authors.lastname: Larsen
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.forename: Maria U
authors.initials: MU
authors.lastname: Martins
authors.forename: Maxine E
authors.initials: ME
authors.lastname: Tan
authors.forename: Morgan R
authors.initials: MR
authors.lastname: Davidson
authors.forename: Santiyagu M
authors.initials: SM
authors.lastname: Savarimuthu
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: McLachlan
authors.forename: Linda H
authors.initials: LH
authors.lastname: Passmore
authors.forename: Morgan N
authors.initials: MN
authors.lastname: Windsor
authors.forename: Belinda E
authors.initials: BE
authors.lastname: Clarke
authors.forename: Edwina E
authors.initials: EE
authors.lastname: Duhig
authors.forename: Ian A
authors.initials: IA
authors.lastname: Yang
authors.forename: Rayleen V
authors.initials: RV
authors.lastname: Bowman
authors.forename: Kwun M
authors.initials: KM
authors.lastname: Fong
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000230:Adenocarcinoma / Q000139:chemically induced* / Q000235:genetics; D000368:Aged; D001194:Asbestos / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002273:Carcinogens; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics; D008297:Male; D016273:Occupational Exposure; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D012333:RNA, Messenger; D001194:Asbestos; D051722:ADAM Proteins; C410224:ADAM28 protein, human