Study
PLCO
(Learn more about this study)
Project ID
2012-0247
Initial CDAS Request Approval
Oct 22, 2012
Title
Blood-based gene expression markers for early detection of lung cancer
Summary
Early cancer detection through screening of high risk individuals has great potential to improve survival from lung cancer, which kills 1.3 million people annually. While monitoring the target organ via tissue or imaging remains a focus of many screening trials, the option of a blood test offers practical advantages including noninvasiveness and easy availability. In a pilot study of microarray gene expression from the Environment And Genetics in Lung cancer Etiology (EAGLE) study, we found 8 genes (TGFBR3, RUNX3, TRGC2, TRGV9, TARP, ACP1, VCAN, and TSTA3) whose expression in cells from peripheral whole blood (PWB) distinguished stage I lung adenocarcinoma smoker cases from smoker controls and whose expression in cells from lung tissue of the same cases distinguished tumor from non-involved paired samples. We validated and extended this finding using a independent group of individuals from the EAGLE population (including 80 lung adenocarcinoma cases, 40 squamous cell carcinoma cases and 120 age, sex, and smoking frequency matched controls) by means of a different and more sensitive technique, Real-Time Quantitative PCR (qRT-PCR) [Rotunno M et al., 2011]. Strikingly, 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. Our goal is to test the identified genes as early detection markers of lung cancer in a retroprospective longitudinal repository study, such as the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), using cryopreserved PWB drawn before cancer incidence. mRNA from PLCO blood samples has been previously successfully extracted, purified, and amplified for RT-PCR assays [Landgren O, et al. 2009]. We would use the nanoString technology which is particularly accurate and cost effective for this type of candidate gene study design.
Aims
The specific aim of this proposal is to test a set of previously identified genes as early detection markers of lung cancer in a retroprospective longitudinal repository study using blood drawn before cancer incidence. Specifically, we will use cryopreserved peripheral blood samples from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We will compare the expression in pre-diagnostic samples of 250 smoker lung cancer cases with the expression in 250 age, sex, and smoking frequency matched controls. We will estimate sensitivity and specificity of the candidate blood biomarkers in distinguishing pre-diagnosis lung cancer cases from controls in the high risk smoking population.
Collaborators
Paula Hyland (NCI, DCEG)
Maria Teresa Landi (NCI, DCEG)
Neil E Caporaso (NCI, DCEG)
