Affordable early screening in subjects with high risk of
lung cancer has great potential to improve survival from this deadly disease. We measured gene expression from lung tissue and peripheral whole blood (PWB) from
adenocarcinoma cases and controls to identify dysregulated
lung cancer genes that could be tested in blood to improve identification of at-risk patients in the future. Genome-wide
mRNA expression analysis was conducted in 153 subjects (73
adenocarcinoma cases, 80 controls) from the Environment And Genetics in
Lung cancer Etiology study using PWB and paired snap-frozen
tumor and noninvolved lung tissue samples. Analyses were conducted using unpaired t tests, linear mixed effects, and ANOVA models. The area under the receiver operating characteristic curve (AUC) was computed to assess the predictive accuracy of the identified
biomarkers. We identified 50 dysregulated genes in stage I
adenocarcinoma versus control PWB samples (false discovery rate ≤0.1, fold change ≥1.5 or ≤0.66). Among them, eight (
TGFBR3, RUNX3, TRGC2, TRGV9,
TARP, ACP1, VCAN, and TSTA3) differentiated paired
tumor versus noninvolved lung tissue samples in stage I cases, suggesting a similar pattern of
lung cancer-related changes in PWB and lung tissue. These results were confirmed in two independent gene expression analyses in a blood-based case-control study (n = 212) and a
tumor-nontumor paired tissue study (n = 54). The eight genes discriminated patients with
lung cancer from healthy controls with high accuracy (AUC = 0.81, 95% CI = 0.74-0.87). Our finding suggests the use of gene expression from PWB for the identification of early detection markers of
lung cancer in the future.