RNA Analysis Can Predict Lung Cancer Among Smokers

CHICAGO-A genetic “fingerprint” detectable in the blood is able to predict with 80% accuracy which asymptomatic smokers will develop lung cancer 2 years later, according to investigators who described the test at ASCO 2008 (abstract 1509).

A group of German scientists, led by Thomas Zander, MD, of the University of Cologne, studied the genetic profiles in the peripheral blood of smokers with lung cancer (prevalent cohort) and controls without lung cancer, and generated an RNA fingerprint based on transcriptional changes associated with the cancer. The fingerprint had a 90% sensitivity and 85% specificity for identifying patients with lung cancer, and 88% accuracy.

"What is remarkable is that most of the relevant transcripts are derived from immune response–related genes."

                          - Dr. Thomas Zander

“We think there are lung-cancer-specific expression profiles in the peripheral blood,” Dr. Zander said at an ASCO press conference.

After validating this in a second cohort, they examined records of 25,000 participants in the European Prospective Investigation on Cancer and Nutrition (EPIC) trial, identifying 12 smokers who had developed lung cancer within 2 years of enrolling in EPIC (incident cohort).

Using archived specimens, the researchers applied the RNA fingerprint to the incident cancer cohort and to a matched control group without cancer, looking for the evidence of the marker before the cancers became clinically apparent.

In this cohort, the test predicted the development of cancer with 80% accuracy (P = .05). Sensitivity was 75% and specificity was 85% (P = .0001), Dr. Zander reported.

“What is remarkable is that most of the relevant transcripts are derived from immune response–related genes,” Dr. Zander said. Other enriched genes were related to homeostasis.

The hope is that the RNA fingerprint may eventually be suitable for identifying patients with early lung cancer and predicting risk among smokers.

Julie Gralow, MD, of the University of Washington, Seattle, noted that the findings were preliminary but that “this is a promising lead for a means of early detection of lung cancer.”