Developing new non-invasive methods for the diagnosis of lung cancer

2012

Career Development Award

Mohamed Hassanein, PhD

Vanderbilt University Medical Center

Nashville

Dr. Hassanein is using 164 proteins found only in lung cancer patients to develop a method to test the patient’s blood for its own antibodies to these proteins. His goal is to use these proteins as biomarkers in a blood test that will find lung cancer in its earliest, most treatable stage.

Research Summary

To significantly reduce the deaths from lung cancer, more accurate diagnostic tests are urgently needed to detect the disease early enough and benefit from a surgical cure. We recently identified 164 novel candidate protein markers in lung cancer from extensive shotgun proteomic profiling of Stage 1 lung cancers. These candidate protein biomarkers are abundantly expressed in Stage 1 lung cancer tissues but not in normal counterparts. While standard ELISA-based assays to validate these candidates can be done, this approach is low throughput, very slow and expensive. In this application, we propose to develop and validate a non-invasive diagnostic test for lung cancer based on the detection of autoantibodies directed against our candidate protein biomarkers that are markedly differentially expressed in lung cancer and present in the circulation. More specifically, we propose to establish an assay to detect and quantitate lung cancer autoantibodies directed against new proteomic biomarker candidates. We will validate the diagnostic efficacy of our autoantibody signature in blood samples taken from individuals with Stage 1 lung cancer or matched nodules controls and integrate these findings in the diagnostic setting of patients presenting with lung nodules. Establishing this new approach may ultimately lead to improving the accuracy of the diagnosis of lung cancer when the disease is surgically curable.

Technical Abstract

The development of non-invasive diagnostic tools to detect lung cancer at an early stage is the subject of active investigations because of its enormous potential impact on the number-one cause of cancer-related deaths. We have recently discovered by shotgun proteomics profiling 164 candidate biomarkers that are differentially expressed in stage 1 lung cancer tissue compared to non-malignant matched controls tissues and found in the circulation. Validation of these candidates by traditional methods using western blot or ELISA is a slow, low throughput, and expensive process. In this application, we propose to take advantage of the individual’s immune response to capture and detect autoantibodies directed against these 164 candidate protein targets identified by shotgun proteomics. To achieve this goal, we intend (1) to establish immune-based assays for the detection and quantitation of lung cancer autoantibodies using an indirect ELISA; (2) to validate the diagnostic performance of our autoantibody signature in blood samples from individuals with early-stage lung cancer or matched nodule controls; and (3) to determine whether the diagnostic performance of our panel of autoantibody signatures augments the diagnostic accuracy of known predictive models for the evaluation of lung nodules. These studies may lead to the development and early validation of a new molecular diagnostic tool for lung cancer.

Key words

Adenocarcinoma

Biomarker or biomarker testing

Early detection

Non-small cell lung cancer (NSCLC)

Risk profile

Screening

Squamous cell lung cancer

Stage I

Developing new non-invasive methods for the diagnosis of lung cancer

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