Novel Biomarker Could Aid Early NSCLC Detection

A new study identified the molecule known as N¹,N¹²-diacetylspermine (DAS) as a potential biomarker for early-stage non–small-cell lung cancer (NSCLC). Along with a previously known biomarker, it had a predictive ability above 80%.

Efforts to find predictive biomarkers have increased in recent years. However, “single markers are unlikely to have sufficient performance for implementation in a screening setting, hence the need to explore several discovery platforms to identify markers that provide complementary performance,” wrote study authors led by Oliver Fiehn, PhD, of the University of California, Davis.

This study used a metabolomic approach involving a liquid chromatography/mass spectrometry hydrophilic interaction method to identify novel biomarkers. This was done using serum samples from 100 patients who subsequently developed NSCLC, along with 199 matched control samples. Results were published in the Journal of Clinical Oncology.

The researchers found that the NSCLC serum samples had elevated DAS levels by 1.9-fold. The area under the curve (AUC) for DAS for all NSCLC patients was 0.657, and DAS levels were elevated in all subgroups analyzed. The AUC was less in the serum samples collected a longer period before NSCLC diagnosis (6 to 12 months), at 0.610, than it was in those collected between 0 and 6 months before diagnosis (AUC, 0.710).

They then combined it with the known lung cancer biomarker pro-surfactant protein B (pro-SFTPB), and analyzed both of these markers in a validation set of 108 patients and 216 controls. Both markers were elevated in the patients, and the combination of the two was significantly more predictive than DAS alone (P < .001) and pro-SFTPB alone (P < .001). The AUC for the combination was 0.808, meaning more than 80% of patients would be found using this combination. Again, samples collected closer to diagnosis were more predictive than those collected earlier.

“Assuming a lung cancer annual incidence rate of 0.0625%, as observed in the [National Lung Screening Trial (NLST)] study, and based on the sensitivity of 35% at 95% specificity for the model combining pro-SFTPB and DAS in prediagnostic sera collected within 6 months before diagnosis of lung cancer, the positive predictive value is 4.2%,” the authors wrote. “This compares favorably to the positive predictive value of 3.6% observed in NLST for nodules suggestive of lung cancer by low-dose CT.”