title: A gene expression signature from peripheral whole blood for stage I lung adenocarcinoma.
abstract: 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.
authors: Division of Cancer Epidemiology and Genetics, NCI, NIH, Department of Health and Human Services, Bethesda, MD 20892, USA.
authors: Melissa
authors: M
authors: Rotunno
authors: Nan
authors: N
authors: Hu
authors: Hua
authors: H
authors: Su
authors: Chaoyu
authors: C
authors: Wang
authors: Alisa M
authors: AM
authors: Goldstein
authors: Andrew W
authors: AW
authors: Bergen
authors: Dario
authors: D
authors: Consonni
authors: Angela C
authors: AC
authors: Pesatori
authors: Pier Alberto
authors: PA
authors: Bertazzi
authors: Sholom
authors: S
authors: Wacholder
authors: Joanna
authors: J
authors: Shih
authors: Neil E
authors: NE
authors: Caporaso
authors: Phil R
authors: PR
authors: Taylor
authors: Maria Teresa
authors: MT
authors: Landi
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor