Further Development of an Exhaled microRNA Biomarker of Lung Cancer Risk
Abstract
Lung Cancer Research Program Area of Emphasis: Identify or develop noninvasive or minimally invasive tools to improve the detection of the initial stages of lung cancer. Background: The National Lung Cancer Screening Trial has proven that lung cancer screening can save lives. However, CT (computed tomography) screening strategies as currently devised are very inefficient, as only 1%-2% of all patients screened have lung cancer, and it takes extraordinary efforts, myriad repeat CT scans, and biopsies to diagnose them. This undifferentiated approach entails substantial harm for a large group of individuals screened who really need not be subjected to this, and missed individuals among those who are screened and end up having cancer. In order to increase the efficacy and efficiency of CT screening for early lung cancer detection, one key approach is to first identify those individuals at highest risk. One need not attain the accuracy of a diagnostic test, say >95% sensitive and 95% specific, to attain a highly useful marker for a disease. For example, it is universally agreed that high blood cholesterol as a risk factor for coronary disease is very useful risk biomarker. Yet as a stand-alone test for the presence of actual coronary disease, it performs poorly (often misclassifies people), as many people with high cholesterol do not have coronary heart disease, and many people with low cholesterol do have coronary heart disease. We are looking for such an easily measured risk factor for lung cancer. We wish to do this by directly sampling the "state-of-the-lung-epithelium," by non-invasive means. We are proposing an exhaled breath test to capture specific molecules derived from the lung that are plausibly related to the cancer-development process. These tests are based on a set of small genetic elements called microRNAs, which have been related, among others, to aberrant gene activity underlying some aspects of cancer development. Most other breath tests have been detecting molecules without a plausible relationship to the lung cancer development process. We have piloted this novel coupling of a non-invasive exhaled breath specimen and the accurate measurement of microRNAs in a manner that could allow exhaled microRNAs to serve as markers of lung cancer risk. Some of this work was performed under a Lung Cancer Research Program Concept Award in 2012-2013. We studied 95 individuals (n=45 lung cancer patients and 50 comparable non-cancer control individuals). This initial four microRNA breath test was able to discriminate those with early-stage lung cancer from those without lung cancer approximately 75% of the time. This is in range of good performance for a risk marker, rather than a definitive diagnostic test. Validation of these initial results requires expanded testing in more and larger groups of individuals. In addition to employing a broadened microRNA panel (over 40 different microRNAs), we wish to: (i) expand the study of our first population in the Bronx; (ii) study a second high-risk population (Veterans); (iii) check if trend over time of the biomarker is more informative than a one-time measurement; (iv) check if added value can be had from measuring microRNAs in sputum; and (v) test function of the top discriminant microRNAs. What types of patients will it help? This early detection approach to the general population is designed for early detection in order to prevent people with small nodules from becoming late-stage lung cancer patients. What are the potential clinical applications, benefits, and risks? There is no non-invasive test of lung cancer risk that directly samples the lung, and for which we understand what that measurement means. The potential to use this exhaled test to leverage lung cancer (CT screening) detection is great, particularly in those who have already taken the essential step to quit smoking. The risk of the exhaled is minimal, as it is non-invasive.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610328
Entities
People
- Simon Spivack
Organizations
- Albert Einstein College of Medicine
- United States Army