High-sensitivity array analysis of gene expression for the early detectionof disseminated breast tumor cells in peripheral blood

Citation
Kj. Martin et al., High-sensitivity array analysis of gene expression for the early detectionof disseminated breast tumor cells in peripheral blood, P NAS US, 98(5), 2001, pp. 2646-2651
Citations number
39
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
00278424 → ACNP
Volume
98
Issue
5
Year of publication
2001
Pages
2646 - 2651
Database
ISI
SICI code
0027-8424(20010227)98:5<2646:HAAOGE>2.0.ZU;2-P
Abstract
Early detection is an effective means of reducing cancer mortality. Here, w e describe a highly sensitive high-throughput screen that can identify pane ls of markers for the early detection of solid tumor cells disseminated in peripheral blood. The method is a two-step combination of differential disp lay and high-sensitivity cDNA arrays. In a primary screen, differential dis play identified 170 candidate marker genes differentially expressed between breast tumor cells and normal breast epithelial cells. In a secondary scre en, high-sensitivity arrays assessed expression levels of these genes in 48 blood samples, 22 from healthy volunteers and 26 from breast cancer patien ts. Cluster analysis identified a group of 12 genes that were elevated in t he blood of cancer patients. Permutation analysis of individual genes defin ed five core genes (P less than or equal to 0.05, PERMAX test). As a group, the 12 genes generally distinguished accurately between healthy volunteers and patients with breast cancer. Mean expression levels of the 12 genes we re elevated in 77% (10 of 13) untreated invasive cancer patients, whereas c luster analysis correctly classified volunteers and patients (P = 0.0022, F isher's exact test). Quantitative real-time PCR confirmed array results and indicated that the sensitivity of the assay (1:2 x 10(8) transcripts) was sufficient to detect disseminated solid tumor cells in blood. Expression-ba sed blood assays developed with the screening approach described here have the potential to detect and classify solid tumor cells originating from vir tually any primary site in the body.