New Molecular Biomarkers May ID Lung Cancer

A new biomarker may be able to differentiate between benign and cancerous lung nodules. The biomarker-a panel of the expression levels of three microRNAs from a sample of sputum--was able to decipher between noncancerous nodules and early-stage lung cancer most of the time. The results are published  in Clinical Cancer Research.

Lung nodules are typically detected with a chest CT scan, but it is relatively difficult to discern a malignant versus a non-malignant lung nodule in those patients who have so-called indeterminate solitary pulmonary nodules (SPNs), which lead to overdiagnosis.

“We are facing a tremendous rise in the number of lung nodules identified because of the increasing implementation of the low-dose CT lung cancer screening program,” said Feng Jiang, MD, PhD, an associate professor in the Department of Pathology at the University of Maryland School of Medicine in Baltimore, and author on the study, in a statement. “However, this screening approach has been shown to have a high false-positive rate. Therefore, a major challenge is the lack of noninvasive and accurate approaches for preoperative diagnosis of malignant nodules.

The three microRNA biomarker panel-miR-21, miR-31, and miR-210-when tested for in concert, could be a way to isolate the malignant cases. The study is so far preliminary and further work is needed to identify other molecular biomarkers to add both sensitivity and specificity to the test. Then, a prospective clinical trial is needed to validate the test if it is to be used in the clinic. “We are now applying new technologies to identify additional miRNA sputum biomarkers of lung cancer with the goal of expanding our biomarker panel to generate a test with high efficiency that can be practically used in clinical settings for lung cancer early detection,” said Jiang in a statement.

The authors tested the three-biomarker panel on a cohort of 122 patients who had a detectable lung nodule on a chest CT scan-60 had malignant nodules and 62 had benign SPNs. The test was able to correctly predict whether a patient had lung cancer 82.9% of the time, and correctly predicted that a positive CT scan was not lung cancer 87.9% of the time.

The test is a quantitative reverse transcriptase PCR assay that detects the levels of these three microRNAs in a patient’s sputum sample. Initially, Jiang and colleagues assessed the expression of a panel of 13 different sputum microRNAs that were previously identified as having a different expression pattern in lung cancer patients. All patients provided sputum samples prior to any treatment for their cancer. According to the current study, 30% of patients could not voluntarily cough up enough sputum to be tested and had a sputum induction using a device called a Lung Flute.

The authors then tested the biomarker panel on two independent groups of 136 and 155 patients who had a detectable lung nodule. In these subsequent trials, the three-marker expression test had a sensitivity of 82.1% and 80.5% in the two groups, and a specificity of 88.4% and 86.1%, respectively.

According to Jiang, the current specificity and sensitivity values are not high enough to warrant use of the test in the clinic. In order to not miss a case of lung cancer, the specificity of the test should be almost 100%.

The appeal of such a test is that sputum is easily accessible, making this test-if it works in further trials-very appealing for use in the clinic. Sputum contains cells that have been sloughed off from bronchial epithelial cells, and while cytology of these cells can identify abnormalities of the bronchial epithelium of lung cancer patients, this is not a sensitive enough assay to diagnose patients with lung cancer.

The rationale for the molecular biomarker using sputum is that the molecular aberrations that occur in the epithelium cells of the lung should be well detected using molecular biology methods.