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Blood-Based MicroRNA Signatures Can Distinguish Individuals With Lung Cancer

NEW YORK – MicroRNA signatures appear to distinguish individuals with lung cancer from those with other lung diseases as well as from those without a lung condition, a new study has found.

Researchers led by Andreas Keller from Saarland University in Germany examined whether they could identify people with lung cancer using miRNA signatures from blood samples. Lung cancer affects about 228,000 people a year in the US and has a five-year survival rate just shy of 20 percent, according to the National Cancer Institute.

As they reported in JAMA Oncology today, the researchers uncovered miRNA signatures that could distinguish people with lung cancer from those without cancer in a cohort of more than 3,100 people, with one signature in particular yielding 91.4 percent accuracy.

"The findings of the study suggest that the identified patterns of miRNAs may be used as a component of a minimally invasive lung cancer test, complementing imaging, sputum cytology, and biopsy tests," Keller and his colleagues wrote in their paper.

The researchers enrolled 3,046 individuals in this retrospective cohort study, including patients with lung cancer, other lung diseases, other non-lung diseases, and unaffected controls. The lung cancer subset encompassed both patients with small cell lung cancer and non-small cell lung cancer, as the researchers hoped to identify general lung cancer biomarkers.

Blood samples collected from the participants underwent genome-wide miRNA profiling using human miRNA microarrays.

In this analysis, the researchers examined the ability of miRNA signatures to identify lung cancer patients in three scenarios: to distinguish patients with lung cancer from those without lung cancer; patients with lung cancer from those with non-tumor lung disease; and patients with early-stage lung cancer from those without lung cancer. To do this, they split their cohort into equal-sized training and validation sets.

Within the training set, they uncovered a 15-miRNA signature that could distinguish patients with lung cancer from all other individuals. In the validation set, this signature could diagnose lung cancer with an accuracy of 91.4 percent, a sensitivity of 82.8 percent, and a specificity of 93.5 percent.

Similarly, the researchers uncovered a 14-miRNA signature that could distinguish patients with lung cancer from those with a non-tumor lung disease with 92.5 percent accuracy, 96.4 percent sensitivity, and 88.6 percent specificity.

A third signature of 14 miRNAs could distinguish patients with early-stage lung cancer from all other patients with an accuracy of 95.9 percent, a sensitivity of 76.3 percent, and a specificity of 97.5 percent.

The signatures do include overlapping mirRNAs, the researchers noted. The signatures for the first and second scenarios shared three miRNAs, as did the signatures for the second and third scenarios, while the signatures for the first and third scenarios shared six miRNAs. A number of these — including hsa-miR-205-5p, hsa-miR-564, hsa-miR-1260b, and hsa-miR-1285-3p — have previously been linked to lung cancer.

Though the researchers focused on general lung cancer biomarkers, they noted that the miRNA hsa-miR-30a-5p was best able to tell small cell lung cancer and non-small cell lung cancer apart.

While these findings suggest blood-based miRNA signatures can identify lung cancer patients — including early-stage patients — the researchers noted that a prospective study of a large cohort using an approach that is better suited to the clinic such as RT-qPCR or ELISA is needed. They added that these biomarkers should also be evaluated in conjunction with imaging, sputum cytology, and biopsy tests.

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