Blood-based gene expression signatures in non-small cell lung cancer.

Abstract

PURPOSE:

Blood-based surrogate markers would be attractive biomarkers for early detection, diagnosis, prognosis, and prediction of therapeutic outcome in cancer. Disease-associated gene expression signatures in peripheral blood mononuclear cells (PBMC) have been described for several cancer types. However, RNA-stabilized whole blood-based technologies would be clinically more applicable and robust. We evaluated the applicability of whole blood-based gene expression profiling for the detection of non-small cell lung cancer (NSCLC).

EXPERIMENTAL DESIGN:

Expression profiles were generated from PAXgene-stabilized blood samples from three independent groups consisting of NSCLC cases and controls (n = 77, 54, and 102), using the Illumina WG6-VS2 system.

RESULTS:

Several genes are consistently differentially expressed in whole blood of NSCLC patients and controls. These expression profiles were used to build a diagnostic classifier for NSCLC, which was validated in an independent validation set of NSCLC patients (stages I-IV) and hospital-based controls. The area under the receiver operator curve was calculated to be 0.824 (P < 0.001). In a further independent dataset of stage I NSCLC patients and healthy controls the AUC was 0.977 (P < 0.001). Specificity of the classifier was validated by permutation analysis in both validation cohorts. Genes within the classifier are enriched in immune-associated genes and show specificity for NSCLC.

CONCLUSIONS:

Our results show that gene expression profiles of whole blood allow for detection of manifest NSCLC. These results prompt further development of gene expression-based biomarker tests in peripheral blood for the diagnosis and early detection of NSCLC.

• Authors: Thomas Zander, Andrea Hofmann, Andrea Staratschek-Jox, Sabine Classen, Svenja Debey-Pascher, Daniela Maisel, Sascha Ansén, Moritz Hahn, Marc Beyer, Roman K Thomas, Birgit Gathof, Cornelia Mauch, Karl-Stefan Delank, Walburga Engel-Riedel, H-Erich Wichmann, Erich Stoelben, Joachim L Schultze, Jürgen Wolf
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 17 Issue 10 Pg. 3360-7 (May 15 2011) ISSN: 1557-3265 [Electronic] United States
• PMID: 21558400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
• Copyright: ©2011 AACR.

Topics

• Adult
• Aged
• Algorithms
• Carcinoma, Non-Small-Cell Lung (blood, classification, genetics)
• Case-Control Studies
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Leukocytes, Mononuclear (metabolism)
• Lung Neoplasms (blood, classification, genetics)
• Male
• Middle Aged
• Oligonucleotide Array Sequence Analysis