Open AccessSignificant Downregulation of Platelet Gene Expression in Metastatic Lung Cancer
Author(s) -
Calverley David C.,
Phang Tzu L.,
Choudhury Qamrul G.,
Gao Bifeng,
Oton Ana B.,
Weyant Michael J.,
Geraci Mark W.
Publication year - 2010
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/j.1752-8062.2010.00226.x
Subject(s) - lung cancer , metastasis , platelet , microarray analysis techniques , gene , downregulation and upregulation , microarray , gene expression , megakaryocyte , transcriptome , cancer research , alternative splicing , biology , platelet activation , cancer , rna splicing , messenger rna , medicine , immunology , pathology , rna , genetics , stem cell , haematopoiesis
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. Clin Trans Sci 2010; Volume 3: 227–232