title: Significant downregulation of platelet gene expression in metastatic lung cancer.
abstract: Platelets play a major role in the metastatic dissemination of tumor cells in vivo . Recent evidence reveals megakaryocyte-derived platelet pre-mRNA is spliced to mRNA and then translated into functional proteins in response to external stimulation. Employing a human lung cancer model, we hypothesized a subset of megakaryocyte/platelet genes exists that are significantly over or underexpressed in metastasis compared with noncancer. Microarray analysis employing platelet mRNA followed by unsupervised hierarchical clustering revealed an expression profile that includes decreased expression of 197 of the 200 platelet genes with the most altered expression (p < 1.0 × 10(-4)). Among the 608 splicing events identified between the metastasis and negative control groups, 33 highly variable genes were identified with between 3 and 13 splicing events each. In conclusion, this preliminary study reveals a platelet-based gene expression signature that differentiates metastatic lung cancer from negative controls on the basis of decreased expression of 197 of the 200 genes with the most altered expression levels. Further study may yield a prognostic tool for future metastasis among subsets of early stage lung cancer patients.
authors.affiliation: Division of Medical Oncology, University of Colorado Denver, USA. calverle@ohsu.edu
authors.forename: David C
authors.initials: DC
authors.lastname: Calverley
authors.forename: Tzu L
authors.initials: TL
authors.lastname: Phang
authors.forename: Qamrul G
authors.initials: QG
authors.lastname: Choudhury
authors.forename: Bifeng
authors.initials: B
authors.lastname: Gao
authors.forename: Ana B
authors.initials: AB
authors.lastname: Oton
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Weyant
authors.forename: Mark W
authors.initials: MW
authors.lastname: Geraci
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D016000:Cluster Analysis; D003710:Demography; D015536:Down-Regulation / Q000235:genetics*; D005091:Exons / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D009362:Neoplasm Metastasis; D025341:Principal Component Analysis; D012326:RNA Splicing / Q000235:genetics