A gene expression signature from peripheral whole blood for stage I lung adenocarcinoma

Melissa Rotunno, Nan Hu, Hua Su, Chaoyu Wang, Alisa M. Goldstein, Andrew W. Bergen, Dario Consonni, Angela C. Pesatori, Pier Alberto Bertazzi, Sholom Wacholder, Joanna Shih, Neil E. Caporaso, Phil R. Taylor, Maria Teresa Landi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1599-1608
Number of pages10
JournalCancer Prevention Research
Volume4
Issue number10
DOIs
Publication statusPublished - Oct 2011

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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